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Curr Microbiol. 2021; 78(12): 4037-4049.

Abstract

Pathogenic bacteria contaminating food or animal feed cause serious economic losses in the health sector as well as is in the agriculture and food industry. The development of bacterial resistance due to the misuse of antibiotics and chemicals, especially in the farm industry, can bring dangerous effects for the global population therefore new safe biological antimicrobial solutions are urgently needed. In this paper, we investigate biological alternatives to antibiotics against foodborne pathogens. The most promising alternatives include antimicrobial proteins, bacteriophages, probiotics, and plant-based substances. Each described group of substances is efficient against specific foodborne bacteria and has a preferred use in an explicit application. The advantages and drawbacks of each method are outlined in the final section. Biological antibacterial solutions are usually easily degradable. In contrast to antibiotics or chemical/physical methods, they are also far more specific. When introducing new antibacterial methods it is crucial to check their safety and ability to induce resistance mechanisms. Moreover, it is important to assess its activity to inhibit or kill in viable but nonculturable cells (VBNC) state and biofilm forms. VBNC bacteria are considered a threat to public health and food safety due to their possibility of remaining viable and virulent. Biological alternatives to antibiotics complete the majority of the advantages needed for a safe and efficient antimicrobial product. However, further research is necessary to fully implement those solutions to the market.

Introduction

Bacterial foodborne diseases are a serious threat when it comes to health safety. WHO states that the global median number of bacterial diseases is 360 million per year, 60% of which are foodborne diseases. A median number of 260,000 people die each year globally due to bacterial foodborne diseases [ 1]. Even though bacterial foodborne diseases can be prevented, they still cause a health and economic burden for every country in the world. The economic cost of all foodborne diseases in the USA is estimated at approximately $10-83 billion annually; therefore, we can assume that at least half of this cost is caused by bacterial pathogens [ 2].

Foodborne bacterial pathogens are usually strictly connected to animal breeding. For example, Salmonella and Campylobacter are often transmitted from poultry; moreover, these bacteria repeatedly display antimicrobial resistance phenotypes [ 3, 4]. In agriculture, pathogenic foodborne bacteria can affect not only the final product but also animal health and production efficiency. For the above reasons, it seems that finding an efficient method to control foodborne bacterial pathogens at the early stages of food production (e.g., during animal breeding), could also decrease the incidence of human infections [ 5]. For years, antibiotics have been widely used for this purpose. However, evidence of bacteria gaining resistance to antibiotics came to light, and currently, after many years of usage, residues of antibiotic drugs are being detected in meat, milk, and egg products [ 6]. Many of the antibiotics that have been administrated is excreted in an active form. Furthermore, there are serious concerns about the transfer of resistance genes from farms to manure, soil, water, and finally to the environment of humans [ 7]. Such a scenario leads to an increase in antibiotic-resistant bacteria and then also to antibiotic-resistant pathogens transmitted to humans via the environment or food. For example Salmonella enterica ser. Typhi infections resistant to ciprofloxacin reached 74% in 2017 from 22% in 1990, while Shigella infections have increased from less than 5% in 2013 to the 24% in 2017 [ 8]. According to the CDC report from 2019 foodborne bacteria are on the highest rise among all resistant bacteria in the last 5 years [ 6]. Therefore, current law concerning agricultural production significantly limits the use of antibiotics for the breeding industry [ 9], especially in the EU and the USA. However, in many other countries, particularly developing ones, there is still a lack of antibiotic usage regulations which can lead to the deepening of the global problem [ 10, 11]. Finding an efficient alternative to antibiotics that could boost the first stages of food production is an urgent need. Importantly, such treatment must be feasible and applicable across large groups of livestock. Furthermore, it should not be toxic to humans. The objectives of the review were to identify and validate the most promising natural non-antibiotic biological methods against foodborne pathogens and to describe their efficiency based on up-to-date experimental findings. Moreover, current consumer choices are progressively more conscious and aimed at natural and ecological food production methods [ 12]. The Discovery of relevant methods and approaches that have been successful and collecting information about current research projects can help to establish a foundation on which future research can be based. For the study, few search engines were used: Web of Science, Scopus, and Google Scholar. The research database was built by the usage of keywords such as biological alternatives to antibiotics, non-antibiotic biological agents, antibiotic-resistant foodborne pathogens.

The literature on the subject indicates a variety of novel methods to fight against bacteria such as antimicrobial proteins (AMPs), plant-derived antimicrobial substances, probiotics, and bacteriophages. Due to the highest occurrence of research dedicated to those groups of substances authors decided to choose them as currently the most promising methods against foodborne bacterial infections both prevention and treatment. Currently, biological alternatives to antibiotics are increasingly used in prevention and therapies against bacterial pathogenic diseases which are reflected in many scientific publications, clinical trials, and commercialized products described in the article.

Antimicrobial Proteins

Naturally occurring AMPs have been found in almost every species and are one of the first forms of organism defense against pathogens. AMPs are a very diverse group of molecules, due to that different classification models exist depending on different features such as structure, mechanism of action, or activity. The majority of them have antibacterial activity on which this review will focus. Mechanism of action is a key element in understanding and facilitating further development of AMPs based drugs. There are two major mechanisms: immune modulation and direct killing. Direct killing can be split into membrane killing and non-membrane killing. Membrane killing is also divided into receptor and non-receptor interactions. Bacterial AMPs usually have an affinity to the receptor molecules while most of the eukaryotes AMPs do not need specific receptors to disrupt bacterial membrane. AMPs form pores in a membrane, causing cell death, preceded by leakage of cellular solutes. Their non-receptor mechanism of action also minimizes the risk of developing resistance by bacteria. Bacterial and eukaryotic AMPs share some features, such as small size (15-50 amino acids), positive charge (from + 2 to + 9) with a significant share of cationic arginine or lysine residues, and are hydrophobic (about 50%) or amphiphobic. Their properties facilitate interactions with the negatively charged bacterial cell wall. In the case of Gram-positive bacteria, peptides interact with lipoteichoic acid and peptidoglycan, displacing divalent ions and at the same time providing binding to the negatively charged lipids located at the outside of the cell membrane. In the case of Gram-negative bacteria, AMPs interact with lipopolysaccharides (LPS) and also displace divalent ions. Eukaryotic AMPs have a broader spectrum of antibacterial activity in comparison to bacterial AMPs and they are much less cytotoxic toward eukaryotic cells. They act as the first natural defense; therefore, the highest expression of AMPs is found in the tissues in contact with the environment such as skin, eyes, respiratory epithelium, lungs, intestines, and urinary tract. Moreover, antimicrobial peptides were also isolated from animals, insects, plants, fungi, etc. The diversity of AMPs along with their antibacterial properties could be utilized in the application of these bioactive molecules as promising drug candidates in the pharmaceutical industry. Those peptides can also act against antibiotic-resistant viable but not culturable (VBNC) pathogens, for example, EmPis-1L peptide efficiently eliminates the antibiotic-resistant VBNC state cells of foodborne pathogenic bacteria such as Escherichia coli O157 and Vibrio parahaemolyticus OS4 [ 13]. AMPs have also the potential to eradicate bacterial biofilms [ 14]. Prominent examples of eukaryotic AMPs with therapeutic potential against foodborne pathogens are ll-37 and α-defensin [ 15], salmine [ 16], lactoferrin [ 17], protamine [ 18], casecidin and isracidin [ 19], fibrinogen [ 20], pleurocidin [ 21], lb-AMP1 peptide [ 22], α-poly-l-lysine (poly-lys), α-poly-l-arginine (poly-arg) and protamines from herring sperm (clupeine sulfate) and salmon sperm (salmine sulfate) [ 23].

Bacteriocins

Bacterial AMPs gained the greatest popularity among AMPs therefore it was needed to describe them as a separate subgroup of potential alternatives. Bacteriocins vary highly in their mode of action and structure; therefore, many different classes and subclasses occur, although in Table ​Table1 1 we propose one of the simplest and most popular classifications. Lately, it is concluded that bacteriocins should be defined as ribosomally produced multi-functional substances of proteinaceous nature, with pronounced antimicrobial activity at certain concentrations [ 24]. They are used by bacteria usually to inhibit other closely related species. They have useful features such as the capability of the rapid killing of bacteria and high potency. They often act at picto- or nanomolar concentrations in contrast to other (eukaryotic) AMPs that require higher molar concentrations. Bacteriocins have a narrower spectrum of activity in comparison to antibiotics and eukaryotic AMPs. They usually act only on a few genera or species closely related to the producer. Due to that fact, they have great potential as a new method for fighting with pathogens while keeping alive the probiotic and commensal bacteria. Other advantages of bacteriocins include activity in a wide pH range and tolerance of high thermal stress. Bacteriocins can be considered efficient antimicrobial agents in past used mainly for food preservation. Currently, the evolution of genetic engineering and proteomics gave access to the development of bacteriocin-based alternatives to antibiotics, especially for the resistance to antibiotic pathogenic bacteria strains.

Table 1

Type

Features

Mechanism of action

Origin from Gram-positive Bacteria

Class I

Thermostable, polycyclic peptides with a molecular weight of less than 5 kDa, contain in their structure unusual amino acids: lanthionine, 3-methyllanthionine, dehydroalanine

Type A lantibiotics-elongated, flexible molecules whose action is based on the formation of pores in the cytoplasmic membrane of sensitive bacterial cells

B-type lantibiotics-rigid, globular molecules with diverse mechanisms of activity. The best known is nisin ( Lactococcus lactis), which has a bactericidal effect on Staphylococcus aureus, Listeria monocytogenes, prevents the development of spores, inhibits the growth of vegetative cells Bacillus, Clostridium

Class II

Non-non-antibiotic bacteriocins-thermostable proteins with a mass less than 10 kDa, divided into 4 subclasses

II A-Pediocin-like bacteriocins-have strong activity against Listeria ssp.

II B-Two-peptide bacteriocins-to achieve the bactericidal activity, the simultaneous action of both peptides is required

II C-Sec-dependent bacteriocins-are secreted using proteins sec

II D-Bacteriocins differing in structure, mechanism of action, and secretion from previous

Class III

High molecular bacteriocins-mainly produced by Lactobacillus and Enterococcus are heat-inactivated

Class IV

Protein-lipid and protein-carbohydrate complexes require the presence of the lipid or carbohydrate portion in the molecule to achieve full activity

Origin from Gram-negative bacteria

Colicins

Majority of them found in E. coli strains

Often consist of a receptor-binding domain, a translocation domain, and a cytotoxic domain

Further subclassification can be based on their mechanisms of action either import mechanism (group A and B) or cytotoxic mechanism (nucleases, pore-forming, M-type, L-type)

Proteins between 20 and 90 kDa in size

Microcins

Small, composed of relatively few amino acids

Peptides with a mass less than 5 kDa-post-translational modified, attack intracellular structures

Peptides with a molecular weight of 7-10 kDa-not post-translational modified, they work by damaging the cell membrane

Currently, bacteriocins are frequently used as antimicrobial preservatives in food products, in three main forms: bacteria cultures, food products containing bacteriocins in the form of crude fermentate, and finally as partially purified proteins. The bacteria cultures producing a chosen bacteriocin and crude fermentates of bacteriocins are supplemented during food production. Commercial examples of such solutions are BioSafe™ (bacteriocin: Nisin A), Bactoferm™ F-LC (sakacin A and pediocin PA-1/AcH), ALCMix1 (plantaricin and carnocin), Bactoferm™ (Leucocin or Sakacin), MicroGARD® (a mixture of different bacteriocins) [ 15]. A flagship example of usage of bacteriocin in the inhibition of foodborne pathogens is nisin Z, also in a purified form (commercial product: Nisaplin®, containing 2.5% nisin) [ 25]. Research showed that orally administered milk with probiotic bacteriocin-producing strains of lactic acid bacteria (LAB), reduced the severity and duration of diarrhea related to Salmonella infection in pigs [ 26]. Bacteriocin pediocin PA-1 reduced vancomycin-resistant Enterococci (VRE) colonization of the intestine of mice [ 27]. Microcin J25 was shown to reduce infection caused by Salmonella in a mouse model [ 28]. Importantly, bacteriocins can effectively fight biofilm formation [ 29], for example, bacteriocin derived from Lactobacillus brevis DF01 can inhibit the growth of biofilms of two popular foodborne pathogens E. coli and S. enterica ser. Typhimurium [ 30]. Moreover, current publications report the effectiveness of LAB producing bacteriocins against antibiotic-resistant Staphylococci [ 31]. Synergistic use of bacteriocins together with bacteriophages is an interesting possibility, research showed the cooperation of those two therapies against food pathogens, e.g., L. monocytogenes [ 32]. What is interesting, scientists described also the activity of new genetically engineered bacteriocins-integrated enterocin CRL35 and microcin V against clinically isolated enterohemorrhagic E. coli and L. monocytogenes [ 33], these findings suggest a further broad potential for the construction of novel bacteriocin antimicrobials. Previous works have shown that AMPs can be produced in plants thanks to currently available genetic engineering tools, this gives a new opportunity for the efficient production of them [ 34]. AMPs genes expressed in the edible plants could be also an alternative to the addition of antibiotics or other antimicrobials to the feed. Optimization of such technology would allow the prevention and treatment of bacterial foodborne infections, especially in livestock.

As described above success stories highly increased interest in bacteriocins as safe alternatives for antibiotics. The number of AMPs was positively tested for antimicrobial properties against foodborne pathogens, although a continuation of research is necessary to deploy them on a greater scale for their utilization as alternatives to antibiotics. Moreover, it is crucial to evaluate the possibility of increasing bacterial resistance to AMPs. The development of antimicrobial peptides for clinical and commercial use still has some weaknesses, such as high production costs. Yet novel and efficient methods of peptide and protein production, e.g., expression of recombinants in plant cells are described with promising results. Moreover, current studies on bacteriocins are very optimistic and suggest that bio-engineering methods can lead to even more efficient and dedicated applications of bacteriocins. Proteolytic digestion in the intestinal tract may affect bacteriocin activity, due to this their delivery procedures are one of the most challenging parts of their application. For example, the development of micelle nanocarriers for nisin can broaden the applicability of foodborne pathogens treatment [ 35] as well as encapsulation of bacteriocin can increase its antibacterial activity against pathogens [ 36]. Thus, research on bacteriocins and AMPs generally will be crucial for further practical use, production, and their application as alternatives to antibiotics by themselves or in synergistic use with probiotics and bacteriophages.

Bacteriophages

Bacteriophages are bacterial viruses that act as natural predators of bacteria making them a specifically tailored weapon. Even though already at the beginning of the twentieth century, phages were known for their antibacterial properties, only after the emergence of widespread multi antibiotic-resistant strains, research and clinical trials of bacteriophages were undertaken again on a larger scale. Phage therapy relies on the natural mechanism of bacteria cell lysis at the site of infection. However current biotechnological advances fairly broadened the range of potential bacteriophage therapeutics by the usage of purified lytic proteins or engineered phages [ 37].

Production of bacteriophages has a long history, the best-known phages are in the area of veterinary medicine, especially applicable to living farm animals [ 38]. In parallel, many clinical trials of phage therapy are now being assayed in humans [ 39]. They can be effective alone or increase low antibiotic concentration effectiveness, for example in the treatment of Staphylococcus aureus [ 40]. An interesting example of bacteriophage and bacteriocin cooperation is the successful control of E. coli both in vitro and in a mouse model by the receptor-binding domains of colicin A with an E. coli phage lysin [ 41]. Many promising results have been obtained in the last several years in defeating pathogens such as S. aureus [ 42], foodborne E. coli [ 43], and S. enterica ser. Typhimurium [ 44]. Interestingly, research on encapsulation of phages allowed to increase the effectiveness of oral therapy for both animals and humans mainly by decreasing gastrointestinal enzyme digestion [ 45, 46]. Another promising development is the genetic engineering of phages leading to the elimination of immunodominant epitopes and decreasing unwanted immune response during therapy, moreover, such manipulations can create precise bacteriophage variants against targeted pathogen [ 47, 48]. Veterinary phage vaccines are another interesting concept with encouraging results; however, this approach focuses rather on preventing bacterial infections than its treatment and is based on animal immune response system therefore it would not be further developed in this review [ 49]. The food industry is the second important area of phage application in particular the meat and raw animal production [ 50]. For example, a cocktail of specific bacteriophages effectively decreased the amount of E. coli bacteria in previously bacteria-inoculated meat samples [ 51]. Similarly, a mixture of bacteriophages isolated from chicken feces decreased the presence of S. enterica ser. Enteritidis on previously inoculated chicken skin [ 52] and S. enterica ser. Typhimurium on porcine skin [ 53]. Furthermore, bacteriophages can reduce S. aureus presence in milk [ 54]. Additionally, phages can be used also as an antibacterial treatment for plant diseases [ 55] and as an additive to food packaging [ 56].

To summarize bacteriophages have a considerable potential to be used as alternatives to antibiotic treatment. What is more, such therapy alone can be considered organic in regards to farm production [ 57]. Bacteriophages can act also as biosensors in recognizing dangerous VBNC foodborne pathogens, for example, they can distinguish viable and VBNC from dead Salmonella cells [ 58]. Unfortunately, administrative regulations for bacteriophages' use and knowledge about their possible side effects are still rather limited. It is also important to notice that bacteriophage resistance mechanisms can occur as a result of their usage [ 59]. However, strategies to combat the resistance problem are developed, for example, usage of bacteriophage cocktails (mixtures of more than one bacteriophage) decreases the effect of possible resistance mechanisms by targeting various kinds of mechanisms [ 60]. Moreover, reports regarding the spreading of foodborne bacterial resistance due to bacteriophages started to emerge causing questions about the security of their free use [ 61]. Although many successful examples of commercialization: Agriphage (Omnilytics Ltd.), Listex (Micreos, Ltd.), SalmFresh®, ListShield®, and EcoShield® (Intralytix Ltd.), show a foreseeable future for the phage therapy and its administrative regulations [ 62], provided by more research being carried out to facilitate public perception and safety profile [ 63].

Plant-Derived Antimicrobial Compounds

The natural antibacterial properties of plants have been known for centuries; however, only in the last decades, their power to control foodborne pathogens was scientifically confirmed, moreover, they are recognized as promising against antibiotic-resistant bacteria [ 64]. Plants are a natural and rich source of promising biologically active agents. During evolution, plants had to develop a variety of sophisticated strategies to survive continuous attacks of microorganisms in their environment. Because plants do not have cell-based immune responses, they had to create other methods of fighting bacteria. There are many functional compounds in plants such as polyphenols, phenols, micronutrients, phytochemicals, and essential oils. Those substances of plant origin are sometimes referred to in the literature as phytobiotics, especially in the case of animal nutrition [ 65]. These organic substances show a natural antioxidant potential as well as antimicrobial properties. It is estimated that there are over 30,000 active antimicrobial substances identified in plants [ 66]. The majority of essential oils obtained from popular herbs have an antimicrobial activity which is attributed to phenolic and terpenoid compounds and these lipophilic compounds can accumulate in bacterial membranes causing disturbances. Based on their chemical structure they can be classified into a few major groups including essential oils, alkaloids, phenolics (listed in Table ​Table2 2 together with their mechanism of action). The detailed mechanism involved is an important link contributing to the plant antimicrobial studies. Lately, there are innumerable scientific publications involving plant secondary metabolites and their antibacterial properties. Although only a small fraction of them include analysis of the action mode of antimicrobial plant metabolites for further assessment. Thus, leading to incomplete information on the mode of action which currently prevents substitution of antibiotics by plant secondary metabolites [ 67].

Table 2

Antimicrobial group

Mechanism

Essential oils

The mechanism of action on an antibiotic or other microorganisms cells is very complex, it involves, among others, denaturation of membrane proteins, the disintegration of the cell membrane, and cell lysis of the microorganism. They can also cause the inactivation of enzymes involved in membrane and wall synthesis, cellular and cell organelles, interfere with cell membrane permeability and electron flow, inhibit the synthesis of DNA, RNA, uptake of proteins and polysaccharides, participation in metabolic processes, and cell division. Essential oils are passed as substances with high lipophilicity, easily penetrate the wall and cell membrane of microorganisms disrupting the integrity and impairment activities essential for the survival of microbe. It is also believed that one of the possible mechanisms of action of essential oils and plant extracts is inhibiting bacterial cell division

Alkaloids

The mode of action of several alkaloid classes such as isoquinoline and polyamine has been studied extensively fairly recently. It has been reported that isoquinoline such as chelerythrine possesses two mechanisms in inhibiting the growth of bacterial cells; through inhibiting the cellular division and nucleic acid synthesis. Isoquinoline inhibits cellular division by tampering with the FtsZ protein, a protein that is essential for the Z ring formation during cellular division. Besides, the synthesis of nucleic acids is also inhibited as isoquinoline inhibits the action of type I topoisomerases; this prevents the translation of antibiotic-resistant genes, increasing bacterial susceptibility toward antibiotics. Polyamine, on the other hand, compromises the integrity and stability of the cell membrane, increasing the membrane permeability via depolarization, leading to leakage of the cytoplasmic contents and later, cell death

Phenolics

Studies have shown that hydrolyzable tannins such as gallotannin are bioactive through the inhibition of glucosyltransferase which is involved in the formation of biopolymers such as DNA, RNA, and protein. Also, hydrolyzable tannins disrupt the peptidoglycan cell wall and cytoplasmic membrane of a drug-resistant strain of Helicobacter pylori and Candida albicans, leading to the leakage of cellular content and cell death

Organosulfur

The main mechanism involved in the antimicrobial effect is assumed to be the inhibition of thiol-containing enzymes in microorganisms by the rapid reaction of thiosulfinates with thiol groups. Generally, organosulfur compounds show their antimicrobial activity by altering the permeability of microbial cell walls and replacing intracellular and extracellular materials with each other. For example, allicin causes quick and complete inhibition of RNA biosynthesis and additionally a partial inhibition of DNA and protein synthesis

Chosen plants with activity against foodborne bacteria are shown in Table ​Table3. 3 . Especially spices and herbs draw attention while thinking about antibacterial potential.

Table 3

Plant

Activity against

The main group of antibacterial compounds

References

Garlic ( Allium sativum)

Organosulfur compounds (allicin, diallyl sulfides),

Phenolic compounds

[ 78, 79]

Clove ( Eugenia caryophillis)

L. monocytogenes, S. enterica ser. Typhimurium, E. coli O157:H7, Sh. dysenteria, S. aureus, E. coli, and S. enterica ser. Enteritidis

Essential oils

[ 83]

Bay leaf ( Laurus nobilis)

Essential oils

[ 84]

Onion ( Allium cepa)

E. coli, S. aureus

Polyphenols, flavonoids, essential oils

[ 85]

Oregano ( Origanum glandulosum)

Essential oils

[ 86]

Peppermint ( Mentha piperita)

S. enterica ser. Enteritidis

Essential oils

[ 87]

Black Pepper ( Piper nigrum)

S. enterica ser. Enteritidis

Flavonoids, essential oils

[ 88]

Rosemary (Rosmarinus officinalis)

L. monocytogenes, and S. aureus

Essential oils

[ 89]

Sage ( Salvia officinalis)

S. enterica ser. Enteritidis, L. monocytogenes, S. aureus

Essential oils

[ 90]

Thyme ( Thymus vulgaris)

E. coli, S. enterica ser. Enteritidis, L. monocytogenes, S. enterica ser. Typhimurium, E. coli O157:H7, Sh. dysenteria, Bacillus cereus, and S. aureus

Essential oils

[ 92]

Ginger ( Zingiber officinale)

Phenolic compounds, flavonoids (gingerol, shogaol, and zingerone)

[ 66]

For example allicin, a compound isolated from garlic ( Allium sativum), is a broad range growth inhibitor for Gram-negative and Gram-positive bacteria. It affects Escherichia, Salmonella [ 68], Streptococcus, Staphylococcus, Klebsiella, Proteus, and H. pylori [ 69]. All serogroups of E. coli, but especially enterohemorrhagic E. coli (serogroup O157) and enterotoxigenic E. coli (serogroup O8), were proven to be sensitive to the garlic extract [ 70]. Plant derivatives can also act as different antibiofilm factors [ 71]. For example, extracts of Cuminum cyminum [ 72] and Capparis spinosa [ 73] were proven to act as quorum-sensing inhibitors against Gram-negative bacterial pathogens. Capparis spinosa extract inhibited motility and interfered with the production of extracellular polymeric substances and biofilm in E. coli, Proteus mirabilis, Serratia marcescens. A growing body of literature has examined citrus plant extracts as rich in various flavonoids, including apigenin, kaempferol, quercetin, and naringenin which can also inhibit biofilm formation in E. coli O157:H7 [ 74] or repress Salmonella pathogenicity [ 75]. Lately, one of the molecules extracted from the tree Diospyros dendo, known as ursolic acid, gained much attention due to the successful inhibition of E. coli bacterial biofilms in five different E. coli hosts (K-12, JM109, C600, EJ500, and JCB495) [ 76]. The addition of ursolic acid to destabilize biofilms is a promising approach since it is active in low concentrations, this plant-derived compound can be added as a complementary factor to increase the susceptibility of bacterial cells for other antibacterials especially where bacteria are prone to form difficult to target biofilm structures, e.g., in animal production pipelines. Moreover, ursolic acid is non-toxic to hepatocytes. What is important currently there is no evidence that plant extracts could induce a VBNC state in bacteria [ 77].

Phytochemicals isolated from Chinese and Indian herbs function as immunostimulants, for example in aquacultures [ 93]. Studies showed that plant compounds and their derivatives could cooperate with probiotics, both due to their negative impact on pathogens and positive impact on gut microflora [ 94]. However, plant extracts differ from one another as far as the concentrations needed to affect certain bacteria are concerned. It is important to establish common concentrations of plant extracts that have a minimum inhibitory or a minimum bactericidal effect. This could increase the usage of plant extracts as antimicrobial additives in animal feed. However, there are still a few questions that should be examined such as: will animals consume the feed with plant extracts or if there are any side effects of such a diet. Genetically modified plants seem to be an interesting possibility, recombinant DNA technology allows producing food or animal feed that already contains active substances. Minimal processing and avoiding extensive purification costs could provide inexpensive and widely available products [ 95].

Probiotics and Prebiotics

Prebiotics are substances that contribute to the growth of microorganisms that are advantageous for their host. The use of probiotics as agents against foodborne pathogens is becoming increasingly popular. The category of probiotic bacteria is wide; however, main groups can be distinguished such as Lactobacillus, Bifidobacteriaceae, and Streptococcus. Those microorganisms act both as a prevention and control of pathogenic bacteria, supplied to an organism get involved in physiological and immunological processes. In many cases, a pathogen infection is strictly connected to the host's gut state. To open the door for normal and balanced intestinal colonization, the administration of mixed probiotics and commensal bacteria is recommended. Such an approach and was proven to facilitate the gut microflora function by filling down possible niches for pathogenic bacteria. Secondly, they stimulate the immune system and support defense responses to pathogenic bacteria. Mechanisms of probiotics action are presented in Table ​Table4. 4 . Besides that, the vast majority of probiotics also produce bacteriocins.

Table 4

Major mechanisms of probiotic action

Common to many types of probiotics

- Protection against colonization

- Production of short-chain fatty acids; effect on intestinal passage

- Microbiota stabilization/normalization

- Acceleration of enterocyte exchange

- Competition with pathogens

Common for individual species

- Production of B group vitamins (B1, B2, B6, B8, B12), PP-niacin, folic acid, stimulate the formation of organic acids and amino acids

- Production of lactic acid (decreases absorption of toxic substances into the blood)

- Direct antagonism

- Stabilization of the intestinal barrier

- Bile salt metabolism

- Enzymatic activity and carcinogen neutralization

Rare mechanisms (specific to individual strains)

- Immune response modulation

- Production of specific bioactive substances; endocrine and neurogenic effects

In humans, evidence shows that probiotics can decrease infections and antibiotic-associated diarrhea [ 96]. Moreover, some strains of probiotic bacteria showed also antimicrobial activity against foodborne pathogens [ 97]. However, using this technique alone does not seem to lead to the full elimination of pathogenic bacterial infections. Nevertheless, a probiotic approach can reduce cross-contamination and dissemination of infections [ 98].

In agricultural production, probiotics are already used as a feed additive in aquacultures [ 99], in chicken [ 100], pigs [ 101], and cattle [ 102]. Research results on probiotic usage in livestock production, show positive growth response in animals and decreased E. coli and Clostridium amount, bacteria responsible for diarrheal diseases [ 103]. Moreover, current studies suggest that especially combination of probiotics and antimicrobial plant extracts is more effective in preventing foodborne infections than when they are applied separately [ 104]. Probiotics can fight the biofilm formation of pathogenic E. coli [ 105]. However, their effectivity of blocking pathogenic bacterial and fungal biofilms creation is based on a probiotic combination [ 106]. To properly select functional probiotics there can be distinguished major characteristics for the safety and technological usefulness (Table ​(Table5). 5 ). A growing body of literature has examined probiotics being used in animal feed, usually in combination with other compounds, for instance, calves feed with multi-strain Lactobacillus probiotic with a combination of phytobiotics with rosmarinic acid improved their health status (reduced occurrence of diarrhea due to reduced amount of Cryptosporidium, and Giardia duodenalis), starter intake, growth performance, and metabolic status [ 107].

Table 5

Criteria

Required properties

Health safety

* Natural origin

* Isolated from the digestive tract of healthy individuals/animals

* Should show a safe use history

* Lack of bile acid cleaving skills

* No side effects

* Lack of antibiotic resistance genes that are located on unstable elements

Functionality

* Competitiveness to the microflora that inhabits the intestinal ecosystem

* Survivability, metabolic activity, and growth at destination

* Resistant to bile salts

* Resistance to the acidic environment of gastric juice

* Competitiveness for closely related species

* Antagonist activity to foodborne pathogens such as H. pylori, Salmonella sp., L. monocytogenes, and C. difficile

* Resistance to bacteriocins and acids produced by the endogenous microflora that inhabits the intestinal ecosystem

* Adhesion and the ability to colonize specific places in the body

Technological usefulness

* Easy to produce large amounts of biomass

* Viability and stability of desirable probiotic bacteria traits during product preparation and distribution

* High bacterial storage survival in finished food products

* Guaranteeing the desired sensory properties of finished food products

* Genetic stability

* Resistance to bacteriophages

Conclusion

The discovery and development of alternatives to antibiotics are currently critically important. The perfect antimicrobial agents should have a possibly narrow spectrum against pathogens and should not cause significant side effects (e.g., diarrhea, colitis, shortage of commensal bacteria). In Table ​Table6, 6 , biological antimicrobial agents described in the article have been compared with traditional antibiotics in regards to their safety and toxicity profile. Combining a few non-antibiotic approaches can bring positive results in pathogen prevention. Choosing the right method is a multifactor decision based on efficacy, economics, safety for human and animal health, availability of the treatment, and finally the probability of inducing bacteria resistance.

Table 6

Characteristic

Antibiotics

Bacteriocins

Bacteriophages

Plant antimicrobials

Probiotics

Developing methods as effective as current antibiotic treatments can bring positive changes in countries where those drugs are still approved and overused in livestock production. The majority of the proposed non-antibiotic methods were designed for both humans and animals. Farm production of animals is the first step of the food industry and it is highly important for the safety of the final product and human health. What is more, antibiotic use in the agricultural environment should be reduced as soon as possible to stop the development of resistance by bacteria and to keep the antibiotic effective at least against human infections. Otherwise, in the foreseeable future, we will have to face a dramatic shortage of effective antimicrobial agents for preventing and treatment of bacterial diseases.

While developing novel, more specific methods for the prevention of diseases, it seems highly important to test the pathogens for possible resistance mechanisms [ 108]. Another emerging challenge in food antimicrobials is inducing a "viable but nonculturable" (VBNC) state by the popular non-biological food sanitizing methods such as temperature, antibiotics, oxygen availability, and others [ 109]. Bacteria entering the VBNC state represent a serious risk to human health and can induce possible foodborne illnesses. Traditional culture-based methods of foodborne bacteria detection suggest that the tested sample is bacteria-free when in fact pathogens can be present in the VBNC state. Many biological antimicrobial solutions can act as a supplementary treatment to lower the risk of VBNC state in bacteria or inhibit biofilm formation. While testing any new antimicrobial it is important to remember that beyond the CFU method additional methods should be used to check the presence of VBNC state and biofilm formation of bacteria. Furthermore, proper education of individuals using antimicrobials (such as doctors, farmers, food engineers, etc.) is still needed to slow down the processes of gaining resistance by pathogenic bacteria. Also, national and private scientific funding programs should prioritize projects aiming to find efficient alternative strategies for antibiotics. While many countries start to tighten antibiotic regulations, soon it will be necessary to implement alternative substances on a large scale. Due to that, it is extremely significant, especially for the food and breeding industry, to find new, safe, and efficient non-antibiotic solutions against bacterial pathogens.

Author Contribution

EŁ conceived the original idea, designed the paper, and wrote the manuscript. TS was involved in planning and supervised the work.

Declarations

Conflicts of interest

The authors declare no conflict of interest.

Footnotes

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References

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77. Rao AP (2017) Plant antimicrobials: inactivation of foodborne pathogens or induction into the VBNC state and their effects on the sensory properties of organic romaine lettuce. Master Thesis, University of Arizona

91. Dadalioǧlu I, Evrendilek GA (2004) Chemical compositions and antibacterial effects of essential oils of Turkish oregano ( Origanum minutiflorum), bay laurel ( Laurus nobilis), Spanish lavender ( Lavandula stoechas L.), and fennel ( Foeniculum vulgare) on common foodborne pathogens. J Agric Food Chem 52(26):8255-8260 [ PubMed]

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Articles from Current Microbiology are provided here courtesy of Springer

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An Alternative to Antibiotics: Selected Methods to Combat Zoonotic Foodborne Bacterial Infections

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Pathogenic bacteria contaminating food or animal feed cause serious economic losses in the health sector as well as is in the agriculture and food industry. The development of bacterial resistance due to the misuse of antibiotics and chemicals, especially ...

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I can teach how to use Gale for citing sources and saving in drive

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The USDA's Animal and Plant Health Inspection Service has announced 12 awards totaling more than $3.2 million in cooperative agreement funding to create antimicrobial resistance dashboards. These awards will help advance scientific knowledge around antimicrobial resistance through partnerships with the National Association of State Departments of Agriculture, Cornell University, Iowa State University, University of Florida, North Carolina State University, Texas Tech University, University of Illinois, University of Missouri and University of Washington.

Antimicrobial resistance is a global health threat that makes antibiotics and other antimicrobials less effective. Addressing AMR is important to APHIS, along with the agricultural and public health sectors, because antimicrobials are some of our most critical tools for treating serious infections and saving the lives of people and animals. Taking a One Health approach to tackling complex human and animal health challenges such as this is imperative.

Data protection is also important to APHIS. All antimicrobial resistance dashboards developed with his funding are required to include data protections similar to the Confidential Information Protection and Statistical Efficiency Act. Once created, APHIS will use the dashboards to monitor trends in antimicrobial resistance patterns, detect emerging resistance profiles, and better understand relationships between antimicrobial use, animal health management practices and antimicrobial resistance.

These public-private partnerships will improve access to information on antimicrobial resistance in domesticated animals, including livestock, poultry, and companion animals. They will focus on:

Developing antimicrobial resistance dashboards to securely track the emergence and spread of antimicrobial resistant microbes in domesticated animals. Identifying and/or developing methods for protecting data confidentiality with these dashboards. Identifying data user needs and preferences for antimicrobial resistance dashboards. Exploring aspects of data management for antimicrobial resistance dashboards.

These dashboard development efforts complement APHIS' ongoing work on antimicrobial resistance. APHIS' National Animal Health Monitoring System collects and evaluates information voluntarily provided by U.S. farmers and ranchers to better understand antimicrobial use in the context of overall animal health. Our partner labs in the National Animal Health Laboratory Network look for antimicrobial resistance, supporting APHIS' work to monitor for trends and identify new or emerging resistance profiles, assess the continued usefulness of antibiotics over time, and provide actionable guidance to veterinarians, producers and other stakeholders.

Congress directed and provided funding to APHIS to carry out this project as part of USDA's fiscal year 2021 and 2023 appropriations. With its extensive animal health expertise and strong federal, state, tribal and industry partnerships, APHIS plays a critical leadership role in identifying antimicrobial resistance in diseases found in animals, such as livestock and poultry, while protecting the nation's food supply.

Source Citation

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USDA invests $3.2 million in antimicrobial resistance dashboards.

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The USDA's Animal and Plant Health Inspection Service has announced 12 awards totaling more than $3.2 million in cooperative agreement funding to create antimicrobial resistance dashboards. These awards will help advance scientific knowledge around antimicrobial resistance through partnerships with the National Association of State Departments of Agriculture, Cornell University, Iowa State University, University of Florida, North Carolina State University, Texas Tech University, University of Illinois, University of Missouri and University of Washington.

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Bacterial STIs include chlamydia, gonorrhea, and syphilis.

Chlamydia

Chlamydia is the most common STI in the United States and is most common among teens and young adults. For more information on chlamydia, visit the CDC's chlamydia page, and this Chlamydia Fact Sheet (pdf).

Gonorrhea

Anyone who is sexually active is susceptible to gonorrhea. Gonorrhea is especially common among young people between the ages of 15 and 24. For more information on chlamydia, visit the CDC's gonorrhea page, and this Gonorrhea Fact Sheet (pdf)

Syphilis

Syphilis infection is divided into four distinct stages: primary, secondary, latent, and tertiary, and there are different signs and symptoms with each stage of illness. For more information, refer to the Syphilis Fact Sheet (pdf) and visits the CDC's syphilis page

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Bacterial STIs include chlamydia, gonorrhea, and syphilis. Chlamydia is the most common STI in the United States and is most common among teens and young adults. For more information on chlamydia, visit the CDC's chlamydia page, and this Chlamydia Fact Sheet (pdf). Anyone who is sexually active is susceptible to gonorrhea.

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Methicillin-resistant Staphylococcus aureus - or MRSA - is a type of highly drug-resistant bacteria that has been a problem in hospital and health care settings for decades. More recently, MRSA has become a problem among otherwise healthy student athletes. Is your child at risk? What can you do to protect against MRSA infection?

What is MRSA?

MRSA is a type of staph bacteria that has become resistant to the effects of many common antibiotics. This means that the antibiotics that used to kill the bacteria - such as methicillin - no longer work. This makes MRSA infections much more difficult to treat.

MRSA first surfaced in hospitals, where it often caused serious bloodstream infections in people who were sick with other diseases and conditions. Now there are varieties of MRSA that occur in nonhospital settings. These infections typically affect the skin of otherwise healthy individuals - such as student athletes.

What does an MRSA infection look like?

An MRSA skin infection looks like a boil, pimple or spider bite that may be:

These infections most commonly occur at sites where the skin has been broken by cuts or scrapes, or on areas of the skin covered by hair, such as the:

How does MRSA spread?

MRSA is spread by:

Skin-to-skin contact. MRSA can be transmitted from one person to another through skin-to-skin contact. While MRSA skin infections can occur in participants of many types of sports, they're much more likely to occur in contact sports - such as football, wrestling and rugby.

Touching contaminated objects. If drainage from an MRSA skin infection comes into contact with an object - such as a towel, weight training equipment or a shared jar of ointment - the next person who touches that object may become infected with MRSA bacteria.

What can schools do to prevent MRSA infections?

Athletic equipment and locker rooms should be regularly cleaned and disinfected. There's no evidence that spraying or fogging rooms or surfaces with disinfectant works any better than just focusing on frequently touched surfaces - such as wrestling mats, weight training equipment and locker room benches.

Schools, coaches and trainers can also:

Educate student athletes about how to prevent skin infections such as MRSA

Encourage student athletes to practice good hygiene

Encourage student athletes to report any suspicious skin infections to the coach

Refer student athletes who have a suspicious skin infection to a doctor

What can athletes do to prevent MRSA infections?

To help prevent the spread of MRSA infections:

Wash your hands. Use soap and water or an alcohol-based sanitizer. Clean your hands before and after playing sports, using shared weight training equipment, and changing a bandage on a wound.

Take showers. Shower immediately after exercise. Don't share items that touch your bare skin - such as bar soap, razors or towels.

Use barriers. Cover cuts and scrapes with a bandage to keep germs out. Lay a towel down to act as a barrier between your skin and benches in weight rooms, locker rooms, saunas and steam rooms.

Wash your clothing and equipment. Follow the laundering directions for your workout clothing, uniform and equipment. Dry clothes completely in a dryer. Wash your workout clothing and uniform after each use.

If you have a skin infection, what should you do?

Cover the infected area with a clean, dry bandage. Then, go see your doctor. Don't try to treat a skin infection yourself.

It's hard to tell the difference between a skin infection caused by MRSA and a skin infection caused by another type of bacteria. Your doctor can order laboratory tests to determine what kind of bacterial infection you have.

How are MRSA skin infections treated?

Minor MRSA skin infections usually heal after being drained by your doctor. If the infection doesn't heal well or gets worse, your doctor may prescribe antibiotics that are still effective against MRSA. If the infection is severe, you may need to be hospitalized. In rare cases, MRSA infections can become life-threatening.

While your skin infection is healing, keep it covered with a clean, dry bandage at all times. To avoid spreading MRSA to others, wash your hands often, especially after changing your bandage or touching the infection. Don't share clothing, towels or hygiene products with anyone else. Don't use whirlpools, therapy pools or swimming pools until the infection has healed completely.

When can the athlete return to play?

The National Athletic Trainers' Association recommends that skin infections be tested for MRSA, and that an athlete who has MRSA should not be allowed to return to play until:

The athlete has taken an appropriate antibiotic for at least 72 hours

Drainage from the wound has stopped

No new lesions have developed in the past 48 hours

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Show references

1. AskMayoExpert. Methicillin-resistant Staphylococcus aureus (MRSA). Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2018.

2. Methicillin-resistant Staphylococcus aureus (MRSA). Centers for Disease Control and Prevention. https://www.cdc.gov/mrsa/community/team-hc-providers/index.html. Accessed May 1, 2019.

3. Matava M. Sports tip: MRSA infections. American Orthopaedic Society for Sports Medicine. https://www.stopsportsinjuries.org/STOP/Prevent/Injury/STOP/Prevent_Injuries/Injury_Specific.aspx. Accessed May 1, 2019.

4. McKean SC, et al., eds. Antibiotic resistance. In: Principles and Practice of Hospital Medicine. 2nd ed. New York, N.Y: McGraw-Hill Education; 2017. https://accessmedicine.mhmedical.com. Accessed May 1, 2019.

5. Anderson DJ. Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Epidemiology. https://www.uptodate.com/contents/search. Accessed May 1, 2019.

6. Braun T, et al. Community-associated methicillin-resistant staphylococcus aureus infection rates and management among student-athletes. Medicine & Science in Sports & Exercise. 2018;50:1802.

7. Zinder SM, et al. National Athletic Trainers' Association position statement: Skin diseases. Journal of Athletic Training. 2010;45:411.

See more In-depth

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The facts about MRSA, along with tips for protection.

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We all want to make healthy food choices, not only to fuel our busy lifestyles but also to make a positive impact on environmental sustainability and animal well-being. High quality animal-based proteins - such as beef, pork, eggs, poultry and dairy - are an important part of a nutritious, balanced diet. However, you may have concerns about antibiotics given to animals and the impact on your health and the environment.

With so many food choices available today, it can get confusing, especially if you're using food labels to decide what to add to your grocery cart. These labels can often raise more questions than they answer. Are there antibiotics in meat and poultry? Is all meat antibiotic free? Do antibiotics make animals grow faster? We spoke with Dr. Kristen Obbink, a veterinarian and assistant director of the National Institute of Antimicrobial Resistance Research and Education based at Iowa State University in Ames, to find some answers.

Livestock farmers consult with their veterinarians to determine the best treatment for farm animals, explains Dr. Obbink. Just like how we may need antibiotics to feel better, sometimes farmers must use antibiotics to treat farm animals that get sick.

"When our animals get sick, we do need to be able to treat them," she continues. "That's not a good quality of life for that animal if they are having to live with an illness and we can't treat it." Plus, research shows that healthy animals result in safer food, Obbink says.

In addition, because of improved animal health practices, livestock farmers are producing more using fewer natural resources than at any time in history.

For example, pig farmers have reduced their carbon footprint by 7.7% since the 1960s thanks to advancements in genetics, animal nutrition and overall pig care, according to the latest research.

Are antibiotics allowed in meat?

All meat, poultry and dairy foods sold in the U.S. are free of antibiotic residues, as required by federal law.

If a farm animal does get sick and need antibiotics, farmers must follow strict FDA guidelines for the proper dosage, duration and withdrawal time - or in other words, the time between when the animal is treated and when it goes to market, Obbink explains. As an added layer of protection, the U.S. Department of Agriculture samples meat and poultry products to ensure they are free of antibiotic residues.

In the very rare case when a product tests positive for antibiotic residues, it is removed from the food supply chain and never goes to market, Obbink explains. This protects the food system, public health, and you personally.

Are most of the antibiotics sold in the United States used in livestock farming?

Maybe you've read or heard that 70% to 80% of the antibiotics sold in our country are given to farm animals. It's a percentage that is often repeated by the media and by vegan activists. However, that number is almost a decade out of date and based on confusing data from the U.S. Food and Drug Administration (FDA), Obbink says.

Since 2009, the FDA has released an annual report of sales and distribution of antimicrobials sold or distributed to food-producing animals like cows, pigs, and poultry.

The report only collects data on sales, not on actual usage. So veterinarians and farmers may purchase antibiotics, but never administer them to animals. Plus, in both human and animal medicine, antibiotics are administered by weight. It takes more antibiotics, on a per pound basis, to treat a 2,000 pound cow than a 150 pound human.

In addition, there are many more farm animals than humans. For instance, there are approximately 327 million people in the United States, compared to about 9.1 billion chickens raised on U.S. farms. "So it's not apples to apples. You can't just take the (FDA) numbers and compare them directly. You have to consider the caveats that go along with it," Obbink says.

Obbink adds that farmers and veterinarians don't just want to see a decrease in sales of antibiotics. Instead, they are focused on the whole public health picture, she says. "We want to prevent disease in the first place. We are doing a lot of research on antibiotic alternatives. We make sure to implement good vaccine protocols for animals and practice good farm biosecurity. So helping animals stay healthy in the first place," Obbink says.

How can farmers reduce antibiotic usage in farm animals?

Farmers continue to work closely with their veterinarians to protect animal health and overall food safety, using the latest science to guide herd-health decisions, Obbink says.

And just like how I repeatedly wash my hands to keep from getting sick during cold and flu season, farmers take precautions - such as improved animal-care practices, vaccines and strict biosecurity protocols - to help animals stay healthy so they don't need antibiotics in the first place, Obbink says.

Farmers and veterinarians are also exploring alternatives to antibiotics, such as probiotics in animal feed, she says. "This is definitely an area that a lot of research and education efforts are being put into," Obbink says.

A new report from the U.S. Food and Drug Administration (FDA) shows progress in reducing antibiotic use in the food system. Since 2015, sales and distribution of medically important antimicrobials for food-producing animals have dropped 38%, the FDA reported.

It's a significant decline and shows that farmers and their veterinarians have made responsible use of antibiotics a priority, Obbink says. "Farmers want to do the right thing," Obbink says. "They truly care about their animals and the food that they produce. Their families eat that food too. We all want animals to be cared for appropriately and with good welfare and safe and healthy food in the process."

Are antibiotics used to "fatten" cattle, and do they make animals grow faster?

Under new regulations implemented in 2017, the FDA worked with animal drug manufacturers to discontinue the use of medically important antimicrobials for animal growth promotion or feed efficiency. In other words, these antibiotics cannot be used to "fatten" cattle or make animals grow faster.

Farmers can use medically important antibiotics for animal disease prevention, treatment and control, but only with a veterinarian's approval and oversight, as required by the FDA. What does "antibiotic free" or "no antibiotics" mean? All meat, poultry and dairy foods sold in the U.S. are free of antibiotic residues, as required by federal law - whether or not the food is labeled "antibiotic free."

Remember, food labels are about marketing, not about food safety, Obbink says. "We have the safest food supply in the world," Obbink says. "We have very safe food, and using antibiotics responsibly and keeping our animals healthy are important to farmers and veterinarians."

Recently, the USDA's Food Safety and Inspection Service clarified meat and poultry labeling claims. Under the new regulations, USDA-certified organic meats and poultry products can be labeled "raised without antibiotics."

Non-organic meats and poultry can be labeled that it was raised without the use of "sub-therapeutic antibiotics," but only if there is an explanation of what that means. Sub-therapeutic antibiotics are those that are given for a longer period of time and at a lower dose, Obbink says. Typically, when farmers and veterinarians use antibiotics to treat a specific illness, they will use a higher dose for a short period of time, depending on the illness, Obbink explains.

How can I ensure meat is safe to eat?

Consumers also have a role to play in protecting food safety. To ensure that meat and poultry products are safe to eat, follow the basic steps for safely preparing foods: clean, separate, cook and chill. Make sure to use clean utensils and cooking surfaces when cooking. Keep raw foods separate from cooked foods. Cook to a food-safe temperature. And chill leftovers within two hours.

Remember, meat is tested to ensure that it is antibiotic-free. You don't have to worry about cooking to "destroy antibiotics" or about antibiotics affecting human health: they aren't there in the first place. Just focus on making the meat taste great, and cook it to a safe temperature to kill any harmful bacteria!

In addition, be sure to wash your hands for 20 seconds with soap and water before and after handling food.

If you have questions about safe food handling at home, call the USDA Meat and Poultry Hotline at 1-888-MP-HOTLINE (1-888-674-6854). Live food safety experts are available Monday through Friday, from 10 a.m. to 6 p.m. Eastern Time. Expert advice is also available 24/7 at Ask.USDA.gov.

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Are there antibiotics in meat and poultry? Why farmers use antibiotics to treat animals

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USDA testing ensures that meat and poultry are free of antibiotic residue, and farmers cannot use medically important antibiotics to "fatten" livestock.

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antibiotics ... Espanol The U.S. Food and Drug Administration ... today approved safety labeling changes for a class of antibiotics, called fluoroquinolones, to enhance warnings ... informed decision about their use." Fluoroquinolones are antibiotics that kill or stop the growth of bacteria. While ...

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Ear Tubes Vs Antibiotics for ear infections

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Ear Tubes Vs Antibiotics for ear infections

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At a Glance

A study found that placing tympanostomy tubes in young children did not reduce the overall number of ear infections any more than oral antibiotic treatment.

The findings may help to inform guidelines for treating children with recurrent ear infections.

Ear infections are among the most common illnesses in U.S. children. They occur when bacteria or viruses infect the area behind the ear drum called the middle ear. Parts of the middle ear become swollen or blocked, trapping fluid behind the ear drum. This leads to pressure and pain, and can also affect hearing.

Childhood ear infections are often treated with oral antibiotics. But using antibiotics too often can cause bacteria to become resistant, so doctors may wait to see if mild ear infections clear up on their own. Some children experience frequent ear infections. For them, doctors may recommend surgery to place a tiny tube in the ear drum, called a tympanostomy tube, to provide ventilation to the middle ear. This helps to drain fluid and prevent future buildup.

Studies comparing ear tubes to oral antibiotic treatment for recurring childhood ear infections have had mixed results. Most were conducted before the pneumococcal vaccine became standard for young children. This protects against strains of bacteria that commonly cause ear infections.

A research team led by Drs. Alejandro Hoberman at the University of Pittsburgh and Diego Preciado of Children's National Medical Center looked at whether tubes reduced the rate of ear infection compared with treating each infection with an oral antibiotic. The study was funded by NIH's National Institute on Deafness and Other Communication Disorders (NIDCD) and National Center for Advancing Translational Sciences (NCATS). It appeared in the New England Journal of Medicine on May 13, 2021.

Researchers randomly assigned 250 ear infection-prone children, 6 to 35 months of age, to receive either ear tubes and antibiotic ear drops or medical management with oral antibiotics. All children had a history of at least three ear infections within 6 months or at least four within 12 months prior to entering the study. They had also received the pneumococcal vaccine. The children were then followed for two years.

The team found no difference in the study's main measure, the total number of ear infections, between the groups. Though the children in the medical management group received more oral antibiotics, the researchers did not find evidence of increased bacterial resistance in their nose and throat samples. There were also no differences in the percentage of severe infections or impact on the children's quality of life.

Of the 121 children being managed with oral antibiotics, 54 underwent tube placement during the study-35 because of failure of medical management and 19 at the request of the parent. Of the 129 children assigned to receive ear tubes, the parents of 13 declined surgery. Because of these changes, the team conducted a secondary analysis limited to children who remained in their original treatment groups. This analysis found a small benefit to the surgical approach: there were an average of 1.47 ear infections per child in the surgical group compared to 1.72 among those receiving oral antibiotics.

Although the two approaches led to a similar number of ear infections, the team did find some advantages to ear tube placement. Children in this group had their first ear infection an average of two months later than those receiving oral antibiotics. They also had fewer days with symptoms related to their ear infection, other than drainage from the ear.

"We used to often recommend tubes to reduce the rate of ear infections, but in our study, episodic antibiotic treatment worked just as well for most children," Hoberman explains.

Another theoretical reason to resort to tubes is to prevent the development of bacterial resistance, Hoberman adds, "but in this trial, we did not find increased resistance with oral antibiotic use."

-by Erin Bryant

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Ear tubes or antibiotics for repeat infections in children?

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A study found that placing tympanostomy tubes in young children did not reduce the overall number of ear infections any more than oral antibiotic treatment.

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New research by an international team of scientists has found strains of group A Streptococcus that are less susceptible to penicillin and other beta-lactam antibiotics, a finding they say is both surprising and worrisome.

The research, published this week in the Journal of Clinical Microbiology, identified 137 strains of Streptococcus pyogenes with mutations to a penicillin-binding-protein associated with decreased susceptibility to multiple beta-lactams. The analysis further found that the mutations appear to be geographically widespread, and that strains carrying the mutations have the ability to spread between patients.

Group A Streptococcus is most known for its ability to cause acute pharyngitis, also known as strep throat, which affects an estimated 600 million people a year globally. But it can also cause more serious and deadly infections like acute rheumatic fever (which can lead to rheumatic heart disease), scarlet fever, sepsis, and necrotizing fasciitis (flesh-eating disease), and is among the top 10 causes of death from infectious diseases.

Group A Streptococcus infections are typically treated with beta-lactam antibiotics, as they have been for decades. But the study authors warn the findings suggest clinicians may no longer be able to assume beta-lactams will work.

"This is really an important wake-up call that...the party may soon be over," said first study author James Musser, MD, PhD, chair of the department of pathology and genomic medicine at Houston Methodist Hospital. "This may be some important first steps to developing some higher-level resistance."

Universal susceptibility no longer a given

The findings are surprising, Musser said, because, for 70 years, microbiologists and clinicians have been taught that group A Streptococcus is universally susceptible to beta-lactam antibiotics. But in October 2019, a study came out identifying two clonally related and epidemiologically linked S pyogenes strains with mutations in the pbp2x gene and reduced susceptibility to ampicillin, amoxicillin, and cefotaxime.

That study prompted Musser and scientists from Sweden, Norway, Finland, Iceland, and Scotland to analyze a library of 7,025 S pyogenes genome sequences to see if they could find other strains with similar mutations. They focused on isolates from sequence types emm1, emm28, and emm89 -which are the most common causes of strep throat and serious invasive group A Streptoccus infections in the United States and elsewhere.

"They're bad actors, numerically speaking, in human infections," Musser said.

Their analysis found 137 S pyogenes strains-roughly 2% of the strains analyzed-with mutations in the pbpx2 gene that alter the amino acid sequence in the bacteria, resulting in the replacement of one amino acid for another. These mutations likely arose from exposure to beta-lactam antibiotics.

"Although 2% sounds relatively low, the surprise, frankly, is that the number of mutations was so high, and that they [the isolates] were geographically widespread, not only in the United States but in Canada, the Nordic countries, and Scotland," Musser said.

When the researchers performed antimicrobial susceptibility testing on these isolates, testing them against penicillin, ampicillin, and four other beta-lactam antibiotics, they found reduced susceptibility compared with wild-type strains that lack the pbp2x mutation. They also found 16 instances in which strains of the same emm type had an identical mutation. And phylogenetic analysis of those strains revealed that they were clonally related-a finding Musser said suggests the mutations don't prohibit the organism from spreading among people and causing invasive infections.

"They don't cause what we call a detrimental fitness effect, so like the normal group A strep, these strains can spread quite well from person to person," he explained.

But the immediate clinical impact of these mutations, at this point, is unclear. While the mutation-harboring strains were less susceptible to beta-lactam antibiotics, they weren't resistant.

"They do not fulfill the laboratory definition of true resistance to these agents yet," Musser said. Moreover, he added, he and his colleagues don't know what kind of effect these mutation-harboring strains have on patients. But he's concerned about what might happen if some of the more contagious group A Streptococcus strains acquire the resistance mutations.

"If you had high-level resistance in a 'super-spreader,' we would have tremendous problems," he said.

Routine surveillance urged

Musser noted that since the group made this discovery, his lab has started doing routine surveillance for decreased susceptibility to beta-lactams in group A Streptococcus -something that most clinical microbiology labs don't do because of the dogma that beta-lactam susceptibility isn't an issue with the organism. And his co-authors, many of whom are diagnostic lab directors, are doing the same.

"We need to be much more vigilant in this arena," he said, adding that surveillance should be done not just on isolates from severe infections, but also on strep throat isolates. "All the strains we looked at in the study were from serious infections. We don't know what the extent of the problem is in the more common pharyngitis situation."

He also said the findings ultimately underscore the need for a group A Streptococcus vaccine, something that scientists have been working on, in fits and starts, for nearly 100 years. Those efforts have been hampered by the large variety of group A Streptococcus strains.

"We desperately need an efficacious vaccine against group A Streptococcus, because at the end of the day, that's going to be the real solution," he said. "It's the only reasonable long-term approach to controlling this organism."
See also:
Jan 29 J Clin Microbiol abstract

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Mutated Strep strains found with lower antibiotic susceptibility

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New research by an international team of scientists has found strains of group A Streptococcus that are less susceptible to penicillin and other beta-lactam antibiotics, a finding they say is both surprising and worrisome.

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Washington, D.C. - January 29, 2020 - Infectious disease scientists identified strains of group A streptococcus that are less susceptible to commonly used antibiotics, a sign that the germ causing strep throat and flesh-eating disease may be moving closer to resistance to penicillin and other related antibiotics known as beta-lactams.

"If this germ becomes truly resistant to these antibiotics, it would have a very serious impact on millions of children around the world. That is a very concerning but plausible notion based on our findings. Development of resistance to beta-lactam antibiotics would have a major public health impact globally," said James M. Musser, M.D., Ph.D., lead author of the study and chair of the Department of Pathology and Genomic Medicine at Houston Methodist Hospital.

Musser and members of his department collaborated with nearly a dozen institutions across seven countries, and this research appears online in the Jan. 29 issue of the Journal of Clinical Microbiology, a journal of the American Society for Microbiology.

Research published earlier in 2019 describing two related bacterial strains compelled Musser's group at Houston Methodist Research Institute and his collaborators to undertake this sizeable international project. They exploited their genome sequence library derived from 7,025 group A streptococcus strains collected over several decades from countries around the world. Of these, they discovered approximately 2% with gene mutations of interest. The researchers then tested the strains in the clinical microbiology laboratory to confirm their decreased susceptibility to beta-lactam antibiotics.

Long thought to lack gene mutations that may lead to penicillin resistance, the findings of reduced susceptibility in some strains suggest that penicillin and related antibiotic treatments for strep throat may eventually become less effective or completely ineffective. These findings underscore the urgent need for a vaccine that protects humans against group A streptococcus.

"We could be looking at a worldwide public health infectious disease problem," said Musser, the Fondren Presidential Distinguished Chair at the Houston Methodist Research Institute and Houston Methodist Hospital. "When strep throat doesn't respond to frontline antibiotics such as penicillin, physicians must start prescribing second-line therapies, which may not be as effective against this organism."

According to the CDC, group A streptococcus causes 20-30% of sore throats in children and 5-15% of sore throats in adults.

Next steps for the investigative team involve experiments to understand how the mutations arise in human patients, how they may affect human disease, and how they may change the virulence of the germ.

Other researchers collaborating on this paper included Stephen B. Beres, Luchang Zhu and Randall J. Olsen (Houston Methodist Research Institute and Houston Methodist Hospital); Jaana Vuopio and Kirsi Gröndahl-Yli-Hannuksela (Institute of Biomedicine, University of Turku, Finland); Hanne-Leena Hyyryläinen (Finnish Institute for Health and Welfare, Helsinki, Finland); Karl G. Kristinsson (Landspitali University Hospital and University of Iceland, Reykjavik, Iceland); Jessica Darenberg (Public Health Agency of Sweden, Solna, Sweden); Birgitta Henriques-Normark (Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden); Steen Hoffmann (Statens Serum Institut, Copenhagen, Denmark); Dominque A. Caugant (Norwegian Institute of Public Health, Oslo, Norway); Andrew J. Smith and Diane S. J. Lindsay (Glasgow Dental Hospital, School University of Glasgow, Scottish Microbiology Reference Laboratory, Scotland); and David Boragine and Timothy Palzkill (Baylor College of Medicine).

This study was supported in part by grants from the Fondren Foundation, Houston Methodist Hospital and Houston Methodist Research Institute, and the National Institutes of Health (AI139369, AI146771, and AI32956).

The American Society for Microbiology is one of the largest professional societies dedicated to the life sciences and is composed of 30,000 scientists and health practitioners. ASM's mission is to promote and advance the microbial sciences.

ASM advances the microbial sciences through conferences, publications, certifications and educational opportunities. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences.

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Discovery Reveals Antibiotic-Resistant Strep Throat May be Too Close for Comfort

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Infectious disease scientists identified strains of group A streptococcus that are less susceptible to commonly used antibiotics, a sign that the germ causing strep throat and flesh-eating disease may be moving closer to resistance to penicillin and other related antibiotics known as beta-lactams.

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John Green podcast interview with Staph.  The Anthropocene Reviewed

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John Green podcast interview with Staph.  The Anthropocene Reviewed

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Hey, cold open to let you know about something weird: We are making merch. Specifically, we are making a coffee mug that contains my review of coffee mugs, which can be read nowhere else in the world except on the coffee mug. So if you or someone you love would like a coffee mug, or a review of coffee mugs, or better still both, please go to dftba.com. If this works, we'll do more weird merch. Alright, here's the show.

Hello and welcome to The Anthropocene Reviewed, a podcast where we review different facets of the human-centered planet on a five-star scale. I'm John Green, and today I'll be reviewing a micro-organism, staphylococcus aureus, and a rhetorical device called the non-denial denial.

Years ago, I acquired an infection in my left eye socket caused by the bacteria staphylococcus aureus. My vision clouded, and then my eye socket swelled shut, and I ended up hospitalized for over a week.

Had I experienced the same infection anytime in history before 1940, I would've likely lost not just my eye but my life. Then again, I wouldn't have ever lived to acquire orbital cellulitis, because I would've died of the staph infections I had in childhood. Staphylococcus aureus is not a normal part of the human microbiome, but many people--perhaps around a third--are like me nonetheless hosts to colonies of it on our skin or in our nasal passages or in our digestive systems. These colonies are usually harmless, but while anyone can get sick with staph, those of us who live amid it every day are more likely to suffer infections.

When I was in the hospital, the infectious disease doctors made me feel very special. One told me, "You are colonized by some fascinatingly aggressive staph." He told me I wouldn't believe the petri dishes if I saw them, and went on to call my continued existence a real testament to modern medicine.

Which I suppose it is. For people like myself colonized by fascinatingly aggressive bacteria, there can be no hearkening back wistfully to past golden ages, because in all those pasts I would be dead.

In 1941, Boston City Hospital reported an 82% fatality rate for staph infections. I remember as a child hearing phrases like, "Only the strong survive" and "survival of the fittest," and feeling terrified by them, because I knew I was not fit or strong. I didn't yet know that when humanity protects the frail among us, and works to ensure their survival, the human project as a whole gets stronger. Failing to understand that has held our species back for millennia, and in fact still does.

Because staph often infects open wounds, it has been especially deadly during war. Near the beginning of World War I, the English poet Rupert Brooke famously wrote, "If I should die, think only this of me: that there's some corner of a foreign / field / That is forever England." Brooke would indeed die in the war, in the winter of 1915, but not in some corner of a foreign field, but instead on a hospital ship, of a bacterial infection.

By then, there were of course thousands of doctors treating the war's wounded and ill. Among them was a 71-year-old Scottish surgeon, Alexander Ogston, who decades earlier had discovered and named Staphylococcus.

Ogston, who sported a magnificent mustache throughout his adult life, was a huge fan of Joseph Lister, whose observations about post-surgical infection led to the use of carbolic acid and other sterilization techniques. These dramatically increased surgical survival rates--in fact, after visiting Lister and learning from him, Ogston returned to his hospital in Aberdeen and tore down the sign above the operating room that read, "Prepare to meet thy God." No longer would surgery be a desperate, last-ditch effort. It could be safe, and clean, and survivable.

Ogston was so obsessed with Lister's carbolic acid spray that his students wrote a poem about it:

The spray, the spray, the antiseptic spray

A.O. would shower it morning, night and day

For every sort of scratch

Where others would attach

A sticking plaster patch

He gave the spray.

It's alright, but it's no Rupert Brooke.

At any rate, Ogston had good reason to give the spray. His first wife, Mary Jane, had died after childbirth a few years earlier, at the age of 25. There's no record of her cause of death, but most maternal deaths at the time were caused by postpartum infection, often due to staphylococcus aureus. And Ogston had seen hundreds of his patients die of post-surgical infection, so no wonder he was obsessed with antiseptic protocols. Still, he wanted to understand not just how to prevent infection, but also what precisely was causing it. By the late 1870s, many discoveries were being made by surgeons and researchers about various bacteria and their role in infection, but staphylococcus was not identified until Ogston lanced a pus-filled, abscessed leg wound belonging to one James Davidson.

Under the microscope, Davidson's abscess was brimming with life. Ogston wrote, "My delight may be conceived when there were revealed to me beautiful tangles, tufts and chains of round organisms in great numbers."

Ogston named these tufts and chains staphylococcus, from the Greek word for bunches of grapes. And they do often look like grape bunches--plump and just a little bit oblong, and also quite yellowish-green. A few years later, a German scientist noted that there were in fact several species of staphylococcus, and named the one Ogston had found staphylococcus aureus, or the golden staph.

But Ogston wasn't content with just seeing the bacteria. "Obviously," he wrote, "the first step to be taken was to make sure the organisms found in Mr. Davidson's pus were not there by chance." So he set up a laboratory in the shed behind his house and began trying to grow colonies of staph, eventually succeeding by growing them in the medium of a chicken egg. He then injected the bacteria into guinea pigs and wild mice, which became violently ill. Ogston also noted that staphylococcus seemed to be "harmless on the surface" despite being "so deleterious when injected." I have also observed this--insofar as I am not much bothered by having my skin colonized by staphylococcus aureus but find it deleterious indeed when it starts replicating inside my eye socket.

James Davidson, by the way, went on to live another forty years after his staph infection, thanks to a thorough debriding and Ogston's liberal use of the spray, the spray, the antiseptic spray. But staphylococcus aureus remained an exceptionally dangerous infection until another Scottish scientist, Alexander Fleming, discovered penicillin by accident, actually. One Monday morning in 1928, Fleming noticed that one of his cultures of staphylococcus aureus had been contaminated by a fungus, penicillium, which seemed to have killed all the staph bacteria. He remarked aloud, "That's funny."

Fleming then used what he called his "mold juice"--I wish I were making that up--to treat a couple patients, including curing his assistant's sinus infection, but mass production of the antibiotic substance secreted by penicillium proved very challenging.

It wasn't until the late 1930s, a group of scientists at Oxford began testing their penicillin stocks, first on mice, and then in 1941 on a human subject, a policeman named Albert Alexander, who'd been cut by shrapnel during a German bombing raid, and who was dying of bacterial infections--in his case, both staphylococcus aureus and streptococcus. The penicillin caused a dramatic improvement in Alexander's condition, but the researchers didn't have enough of the drug to save him. The infections returned, and Alexander died in April of 1941. His seven-year-old daughter Sheila ended up in a local orphanage.

Scientists began to seek out more productive strains of the mold, and eventually found one on a cantaloupe in a Peoria, Illinois grocery store. That strain eventually became even more productive after being exposed to X-rays and ultraviolet radiation, but essentially all penicillin in the world descends from that mold on that one cantaloupe in Peoria. That's not the astonishing thing about the story, though. The astonishing thing is that after scraping off the mold that became the world's supply of penicillin, the scientists in question ate the rest of the cantaloupe.

Even as penicillin stocks increased--from not enough to save a single human being in 1941 to 21 billion units in 1943 to 6.8 trillion units in 1945--there was growing awareness that the bacteria killed by penicillin were evolving resistance to it, especially staphylococcus aureus. A 1946 Saturday Evening Post article worried that antibiotic use would "unwittingly aid and speed up the subtle evolution forces which arrange for the survival of the fittest microbes." And so it was to be. By 1950, 40% of staphylococcus aureus samples in hospitals were resistant to penicillin; by 1960, 80%. Today, only around 2% of staph a. infections are sensitive to penicillin.

This all happened so, so quickly. 64 years elapsed between Alexander Ogston's discovery of staphylococcus and the mass production of penicillin, and 64 years elapsed between the mass production of penicillin and my 2007 bout with orbital cellulitis. In the end, my infection did not respond to penicillin, or to the next two lines of antibiotics, but did fortunately respond to the fourth. But antibiotic resistance is not only a problem for the future--some 50,000 people in the United States die of staphylococcus aureus infections every year.

How recent is penicillin? That police officer's daughter, Sheila, who ended up in the orphanage--she's still alive. She married an American soldier and moved to California. She's a painter. One of her recent paintings depicts a block of homes in an English village. Ivy grows up along one wall, creeping over the rough stone.

To me, the great mystery of life is why life wants to be. Staphylococcus doesn't want to harm people. It doesn't know about people. It just wants to be, like that ivy wants to spread across the wall, occupying more and more of it. How much? As much as it can. So it's not staph's fault that it wishes to be. Wishing to be is the mark of life, and the glory of it.

Still, I can only give staphylococcus aureus one and a half stars.

After the break, we'll turn our attention to the non-denial denial, but first . . .
AD BREAK
Sometimes, when I am exceptionally despondent about the condition of contemporary political life in the United States, I will turn to history, especially to the politicking of ancient Rome.

There's a famous document called The Little Handbook on Electioneering, purportedly written by Quintus Tullius Cicero, to his older brother, Marcus. Marcus is the famous Cicero, the Roman lawyer and orator who served as Roman consul in 63 BCE. Scholars dispute whether Quintus actually wrote the Little Handbook--it may have been a later creation--but regardless, despite being a couple thousand years old, it is in some ways a very contemporary document. It argues, for instance, that "Men are more taken by look and words than by actual services." It also points out that when someone asks of you something you cannot do, you can either promise to do it anyway or politely refuse. "The latter is the conduct of a good man," the Handbook tells us, "the former of a good candidate."

But what really gets me about The Little Handbook on Electioneering is a paragraph on pointing out the flaws in other candidates, in this case Roman senator Cataline. The Handbook reads, "Why should I speak of him as a candidate for the consulship, who caused Marius, a man most beloved by the Roman people, to be beaten with vine-rods in the sight of that Roman people from one end of the city to the other, forced him to the tomb, rent his frame with every kind of torture, and while he was still alive and breathing, cut off his head?" The Little Handbook goes on to describe Cataline not only as a murderer but worse still as "a man who afterwards lived with actors and gladiators on such terms that the former ministered to his lust and the latter to his crimes." It's one thing to decapitate your brother-in-law. But living with actors who minister to your lust--that's properly disqualifying.

The Handbook also says that people "would rather you told them a civil lie than give them a point-blank refusal." It's a coincidence, but a wonderful one, that civil lies sounds so much like civilize.

I first heard the term "non-denial denial" while reading Bob Woodward and Carl Bernstein's book All the President's Men about the Watergate cover-up that led to President Richard Nixon's resignation back in 1974. Nixon's press secretary Ronald Ziegler regularly released denials that did not actually deny the accusations in question. Ziegler once said, for instance, "Stories are being run based on hearsay, innuendo, guilt by association," which is a criticism of the press but not a denial of the story.

In the decades since, the non-denial denial has become almost beautiful in its linguistic sophistication. Like after the National Enquirer published reports of 2008 Democratic presidential hopeful John Edwards having a child outside of his marriage, Edwards said "That's tabloid trash. They're full of lies." But that comment is carefully worded to say that tabloids often spread misinformation without saying that they were in this case spreading misinformation. Edwards did eventually say, "The story's just false," but false is a word that pops up in many non-denial denials. It's useful because it's vague--like maybe the story is false because you didn't actually have a child with your mistress whom you supported with funds from campaign donations, or maybe the story is false because it claimed you boarded an airplane at noon when in fact you boarded it at 12:06 PM.

The best non-denial denials sound like broad statements but secretly aren't. Former U.S. President Bill Clinton issued what seemed to be a blanket denial, when he said of an affair, "I did not have sexual relations with that woman," but it turned out that he had an extremely specific definition of "sexual relations" in mind when uttering those now-famous words.

But there are many other varieties of non-denial denials. You can answer a question different from the one you were asked, as when Chris Christie responded to allegations he'd closed a bridge for politically motivated reasons by saying, "I am not a bully." Or you might use certain words to describe an accusation that seem like denials but really aren't. My favorite is "outrageous," as when U.S. Senator Marco Rubio described as "outrageous" a report that he mischaracterized his family history. Many things are outrageous but still true, especially in politics.

Ultimately, I think language exists to facilitate communication, to make my thoughts transparent to you and yours transparent to me. But language can also be used to make the past and the present confusing, and even opaque. And in those senses, the non-denial denial is a failure of language. Still, in the end, I think I prefer non-denials denials to the pure lies that some politicians are happy to tell. The current U.S. President seems not to be very interested in linguistic acrobatics, and instead is content simply to lie--both when it comes to big matters, like claiming that China pays for U.S. tariffs on Chinese goods, and also when it comes to ridiculously small matters, like the fact that he used to serve as his own spokesperson under the pseudonym John Barron.

Of course, the President isn't the only politician to take stretching the truth to the level of breaking it, but he is currently the most prominent. I suppose one could argue that it's better to live with provably false statements than the intentional obfuscation of non-denial denials. And I realize that no American politician has, as of yet anyway, decapitated a political rival and paraded around town with a disembodied head. Still, I'll confess that the times in which I find myself have left me a little nostalgic for the days of civil lies.

I give non-denial denials two stars.

Thanks for listening to The Anthropocene Reviewed, which was written by me, edited by Stan Muller, and produced by Rosianna Halse Rojas and Tony Phillips. Joe Plourde is our technical director. Hannis Brown makes the music. The pairing of today's episode was inspired by a quote apparently misattributed to Cicero: "Politicans are not born. They are excreted." Penicillin really is excreted, though. Thanks to Megan, Austin, and Deepti for suggestions reviews of penicillin. I want to leave you today with my favorite fact that didn't make it in to today's reviews: Alexander Ogston, the Scottish surgeon who discovered staphyloccocus, raised some wondrously radical children, including his daughter Helen, who was a famous British Suffragette. In 1908, Helen attempted to give a speech at London's Royal Albert Hall arguing that women should have the right to vote. Male stewards tried to pull her off the stage violently; one pressed the lit end of a cigar to her wrist. Helen Ogston responded by pulling out a dog whip and whipping the men. It would be another 20 years before women in Britain had the same voting rights as men. Just as the daughter of that policeman treated with penicillin is still alive, there are British women still alive who were born in a country where women could not vote. History is new, my friends, and we are all of us making it all the time together.

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Staphylococcus Aureus and the Non-Denial Denial | The Anthropocene Reviewed | WNYC Studios

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John Green reviews staphylococcus aureus and the non-denial denial.

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U.S. Antibiotic Awareness Week is November 18-24, 2023.

USAAW is an annual observance that raises awareness of the threat of antibiotic resistance and the importance of appropriate antibiotic use.

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Help slow the spread of antibiotic resistance. Participate in our effort to promote correct antibiotic use.