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Edmond Nocard was French veterinarian born in 1850.

Edmond Nocard’s extensive work secured him international recognition during his own lifetime. He developed methods for harvesting blood serum and tuberculosis bacillus cultures, studied the bacterium responsible for mastitis in cows and discovered mycoplasma and identified it as the cause of bovine pleuropneumonia. He turned tuberculin and mallein into major weapons in the battle against bovine tuberculosis and equine glanders, two bacterial diseases that were transmissible to humans and decimating livestock at the time… One genus of bacterium was called Nocardia in his honor, after his discovery of the agent responsible for bovine farcy (N. farcinia). Another Nocardia can cause nocardiosis in humans, affecting mainly immunocompromised individuals. Nocard also contributed to a major medical breakthrough after his death, by giving his student Camille Guérin a bovine tuberculosis bacillus culture that gave rise to the BCG: Bacillus Calmette-Guérin.

References:

https://www.pasteur.fr/en/institut-pasteur/history/edmond-nocard-discoverer-nocardia-bacterium

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Edmond Nocard, discoverer of the Nocardia bacterium

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In 1868, Edmond Nocard enrolled in the Veterinary School of Alfort, where he was to spend most of his career. His studies were interrupted by the Franco-Prussian War in 1870. He graduated in 1873 as class valedictorian and became a veterinarian and then head of the clinical department in Alfort.

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DNA-based typing methods, including pulsed-field gel electrophoresis and randomly amplified polymorphic-DNA analyses, have been used to characterize clinically related N. asteroides strains and have shown that clinical isolates of N. asteroides are genetically heterogeneous.

N. asteroides is also involved in the saprophytic digestion and recycling of plant material in natural environments . The primary reservoir of N. asteroides is thought to be the soil, but this organism can also be found in lake and marine sediments. However, there is little published information on the genetic diversity of N. asteroides strains associated with these natural habitats . The purpose of the present study was to characterize and differentiate N. asteroides strains isolated from both terrestrial and aquatic environments by using the repetitive extragenic palindromic (REP)-PCR fingerprinting technique, in which PCR amplification of the DNA between adjacent repetitive extragenic elements is used to obtain DNA fingerprints . REP-PCR has recently proven to be highly discriminatory for subtyping or strain classification of several bacterial species.

Nocardia asteroides is a species of Nocardia. It belongs to the order Actinomycetales and the family Nocardiaceae. The genus Nocardia was divided into 7 groups, including N. asteroides.

Yamamura H, Hayakawa M, Nakagawa Y, Iimura Y. Characterization of Nocardia asteroides isolates from different ecological habitats on the basis of repetitive extragenic palindromic-PCR fingerprinting. Appl Environ Microbiol. 2004 May;70(5):3149-51. doi: 10.1128/AEM.70.5.3149-3151.2004. PMID: 15128581; PMCID: PMC404384.

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Gram-staining (Brown-Brenn modification)

Presence of gram-positive branching or partially branching, filamentous bacilli often with beaded appearance suggest the presence of actinomycetes.

Modified acid-fast staining (Kinyoun method)

Nocardia spp. are partially acid-fast and appear as branching and filamentous red-colored acid-fast bacilli when stained by a modified acid-fast staining method (using 1% sulfuric acid as decolorizer).

Check out this article about the structure of the N. asteroides cell wall! https://pmc.ncbi.nlm.nih.gov/articles/PMC235848/

Picture credit: https://www.researchgate.net/figure/Nocardia-asteroids-staining-and-culture_fig1_323376151

Information credit:

https://microbeonline.com/nocardia-properties-pathogenesis-diagnosis/

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Week 9: Disease Transmission and Epidemiology

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Week 9: Disease Transmission and Epidemiology

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Disease Transmission:

Nocardia asteroides disease transmission primarily occurs through inhalation of dust containing the bacteria or direct inoculation via cuts or scrapes when contaminated soil or water enters the body. The disease is considered an opportunistic infection, meaning it typically affects individuals with weakened immune systems. Risk factors include exposure to contaminated soil, gardening without protective gear, and having a weakened immune system, such as from organ transplants or other conditions.

The bacteria's natural habitat is soil, decaying vegetation, and salt- and fresh-water aquatic environments. It has been isolated from common sources, such as house dust, swimming pools, tap water, wastewater, beach sand, compost, and manure. It has also been isolated on dust particles obtained from air samples.

Epidemiology:

Nocardia species are found worldwide in both temperate and tropical climates, and infections in humans have been reported on all continents except Antarctica. The distribution of the varying Nocardia species is also dependent on geographic location.

Due to lack of systematic surveillance, the true prevalence of nocardial infections is unknown. In the early 1970s, the incidence in the United States was estimated to be approximately 500 to 1000 new cases per year. The current incidence is likely to be higher as the overall United States population has increased alongside our capability to diagnose infection. Further, prevalence estimates of immunosuppression among adults in the United States utilizing the National Health Interview Survey have increased from 3 percent of adults in 2013 to 7 percent in 2021.

Morbidity rate is high in immunocompromised people. 500-1000 cases per year.

Mortality rate for immunocompromised individuals is 19-22%.

References:

https://www.cdc.gov/nocardiosis/about/index.html

https://www.sciencedirect.com/topics/medicine-and-dentistry/nocardia-asteroides

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Week 4: Metabolism and Growth Requirements

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Week 4: Metabolism and Growth Requirements

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Nocardia asteroides is a chemo-organotrophic bacterium with an oxidative type of metabolism when utilizing carbohydrates. It is an aerobic gram-positive actinomycete that is saprophytic, non-spore-forming, and partially acid fast. Members of the genus Nocardia exhibit metabolic versatility, including the production of secondary metabolites with various biological activities.

Nocardia asteroides is an organism that grows on various media, including brain heart infusion agar, sheep blood agar, chocolate agar, and Sabouraud dextrose agar (SDA). Nocardia asteroides grows in a nutrient broth. It is found in the environment and can be inhaled or ingested by immunosuppressed or immunodeficient patients.

References

https://www.pathologyoutlines.com/topic/microbiologynocardia.html

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Week 5: Genome Analysis and Virulence Factors

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Week 5: Genome Analysis and Virulence Factors

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The genome for N. asteroides is almost 7 million nucleotides long, it has a GC% of 70. It has a single circular chromosome.

The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells. The virulence of most nocardiae is growth stage dependent, and the relative degrees of pathogenicity correlate with specific changes in the structure of components of the cell wall during the growth cycle. The most important of these is the glycolipid, trehalose dimycolate. In addition, virulent strains of N. asteroides secrete a unique superoxide dismutase and contain increased amounts of catalase that protect these organisms from the oxidative killing mechanisms of phagocytes. Furthermore, Nocardia should be considered a primary pathogen of the brain since blood borne organisms have a specific predilection for this region of the body. Studies have shown that there is specific binding or adherence to subpopulations of capillary endothelial cells in regions of the brain. Following attachment, the endothelial cells phagocytize these nocardiae and they pass through the basement membrane to enter the brain parenchyma. The nocardiae invade neurons and grow within most types of brain cells without inducing an inflammatory response. The mechanisms for adherence, invasion and growth within the brain are not known.

https://www.atcc.org/products/19247

https://link.springer.com/chapter/10.1007/978-94-011-0746-4_39

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Growth of Nocardia spp. isolated from TB suspects on three different media used in this study (a) LJ medium (see arrows), (b) Blood agar plate and (c) Chocolate agar plate

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Week 6: Biochemistry and Diagnostic Tests

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Week 6: Biochemistry and Diagnostic Tests

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Nocardiae species are non-motile, catalase-positive, and utilize a number of sugars oxidatively. Various biochemical tests are done for species identification such as:

1. Decomposition of casein, hypoxanthine, tyrosine

2. Growth in lysozyme

3. Acetamide utilization

4. Growth at 45°C for 3 days

5. Acid from rhamnose

6. Gelatin hydrolysis

7. Opacification of Middlebrook agar

The genus Nocardia comprises over 130 species of soil-dwelling actinomycetes, many of which are opportunistic pathogens. Beyond their pathogenicity, Nocardia exhibits significant biosynthetic potential, producing an array of diverse antimicrobial secondary metabolites. This review highlights notable examples of these compounds and explores modern approaches to unlocking their untapped biosynthetic potential. As a relatively underexplored genus, Nocardia represents a promising source for new antibiotics to combat the growing resistance crisis.

Brown-Elliott, B. A., Brown, J. M., Conville, P. S., & Wallace, R. J., Jr (2006). Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clinical microbiology reviews, 19(2), 259–282. https://doi.org/10.1128/CMR.19.2.259-282.2006

Hoza AS, Mfinanga SGS, Moser I, König B. Isolation, biochemical and molecular identification of Nocardia species among TB suspects in northeastern, Tanzania; a forgotten or neglected threat? BMC Infectious Diseases. 2017 Jun;17(1):407. DOI: 10.1186/s12879-017-2520-8. PMID: 28595598; PMCID: PMC5463502.

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Pulmonary Nocardiosis

Pulmonary nocardiosis can occasionally occur through gastrointestinal tract especially through appendix rarely pulmonary infection follows dental procedures or peri odontal infection. Symptoms include cough, fever, dyspnea, chest pain, weight loss and hemoptysis. It can present as an acute, sub-acute or chronic disease with remissions and exacerbations.

CNS Associated Nocardiosis

The most common extra pulmonary site for Nocardiosis is CNS. It is uncommon but clinically important disease as it is associated with high mortality. It accounts for 15-50% of nocardiosis and 2% of brain abscesses. It can affect the brain or spinal cord. It occurs along with pulmonary disease or as isolated disease. It usually occurs in immunosuppressed individuals. The presentation is usually with headache, nausea, vomiting, focal neurological deficit and seizures or as cord compression. Radiological features are nonspecific and may involve brain or cord as parenchymal lesions. Multifocal ring enhancing lesions are the dominant features of brain. The most common pathology is single or multiple brain abscess and the other pathologies include meningitis or granuloma.

Cutaneous Nocardiosis

Cutaneous nocardiosis usually occurs in immunocompetent individuals. N. brasiliensis is the most common species isolated from the majority (approximately 80%) of cases, though the disease can be caused by any species.

Pathology

The biopsy sections stained with hematoxylin and eosin (H&E), usually show abscess with predominant neutrophilic infiltrate. A few foreign body giant cells, lymph mononuclear cells and rarely a granuloma formation may be seen, especially in mycetoma of cutaneous nocardiosis. The granules of nocardia are white and small, measuring 0.5 to 1µm in diameter. In mycetoma, compact granules are formed, similar to those observed for the anaerobic actinomycetes. Rarely, the grains show peripheral intense eosinophilic material, representing Splendore-Hoeppli phenomenon. H&E shows the tissue reaction and the grains but the filamentous nature of the bacteria is not appreciated. Nocardia microorganisms are filamentous rods that show right angled branching both in culture and in tissues. The filaments are gram positive and stained with Brown & Brenn (equivalent of gram stain) stain on tissue sections. The filaments are weakly acid fast and are stained with the modified Kinyoun or the Fite Faraco staining methods. Gomori’s methenamine silver stain also delineates the filaments.

References

https://www.jscimedcentral.com/public/assets/articles/footankle-2-1040.pdf

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Nocardiosis treatment typically involves trimethoprim/sulfamethoxazole (TMP/SMX) or high doses of sulfonamides, with the need to maintain specific blood concentrations due to the slow response. In immunocompromised patients or those with disseminated disease, TMP/SMX may be combined with other antibiotics until further testing is completed. Alternatives are available for those with sulfonamide hypersensitivity or refractory infections. Localized abscesses generally require incision, drainage, and surgical debridement.

Cotrimoxazole, linezolid, and amikacin are active against >95% of Nocardia isolates.

In a retrospective review of 765 isolates submitted voluntarily to the United States Centers for Disease Control and Prevention (CDC) between 1995 and 2004, 42 percent were resistant to trimethoprim-sulfamethoxazole (TMP-SMX) and 61 percent were resistant to sulfamethoxazole. This incidence of resistance is significantly higher than in other reports. There are limitations to this study, with the authors concluding that the presented data are probably not representative of all United States cases. As an example, patients who were failing treatment due to resistance may have been more likely to have had their isolates sent to the CDC than patients with susceptible isolates who were responding to treatment.

References

Lafont, E., Conan, P. L., Rodriguez-Nava, V., & Lebeaux, D. (2020). Invasive Nocardiosis: Disease Presentation, Diagnosis and Treatment - Old Questions, New Answers?. Infection and drug resistance, 13, 4601–4613. https://doi.org/10.2147/IDR.S249761

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Patient Details:

•44 year old male, history of heavy smoking, elicit drugs and alcohol use

•2 months prior had necrotic lesion in the upper left quadrant of the lung

•PPD and TBN

•HIV Negative

•Anorexia – 20 pound weight loss

•Trouble breathing

•Mass in left lung

•Bell’s palsy on the left side of body

•Parapalegia

•Masses in the brain

•Patient lost vision in left eye due to Bell’s palsy

•Brain lesions dissemination and spinal involvement resulted in quadriplegia

•Bed sores

Diagnosis - N. asteroides and Nocardiosis from exposure to environmental samples.

References

•Antoni Torres, Rosario Menéndez, Richard G. Wunderink, 33 - Bacterial Pneumonia and Lung Abscess,Editor(s): V. Courtney Broaddus, Robert J. Mason, Joel D. Ernst, Talmadge E. King, Stephen C. Lazarus, John F. Murray, Jay A. Nadel, Arthur S. Slutsky, Michael B. Gotway, Murray and Nadel's Textbook of Respiratory Medicine (Sixth Edition), W.B. Saunders, 2016, Pages 557-582.e22, ISBN 9781455733835,https://doi.org/10.1016/B978-1-4557-3383-5.00033-6. (https://www.sciencedirect.com/science/article/pii/B9781455733835000336)

•W. Putnam Wolcott, Jacek M. Malik, Christopher I. Shaffrey, Mark E. Shaffrey, John A. Jane, CHAPTER 3 - Differential Diagnosis of Surgical Disorders of the Spine, Editor(s): EDWARD C. BENZEL, Spine Surgery (Third Edition), Churchill Livingstone, 2005, Pages 33-60, ISBN 9780443066160, https://doi.org/10.1016/B978-0-443-06616-0.50008-0. (https://www.sciencedirect.com/science/article/pii/B9780443066160500080)

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