Sources:

https://www.ncbi.nlm.nih.gov/books/NBK532894/

https://www.mayoclinic.org/diseases-conditions/lyme-disease/symptoms-causes/syc-20374651

• Amedee Borrel distinguished Borrelia from other spirochetes, and this discovery was later named after the microbiologist.

• The Lyme disease rash was recognized by a dermatologist Arvid Afzelius--he also hypothesized the tick link

Discovery of Lyme Agent:

• Lyme disease was first identified in 1970s after several arthritis cases followed by tick bites. Yale students discovered the link

• In Shelter Island, NY 1981, Dr. Burgdorfer was examining ticks and identified spirochetes in the gut of the ticks. He later published his discovery and formally described the species as Borrelia Burgdorferi.

Sources:

https://www.ncbi.nlm.nih.gov/books/NBK532894/

https://pmc.ncbi.nlm.nih.gov/articles/PMC385417/

• Clades within genus:

  • Borrelia Burgdorferi Sensu Lato

  • Relapsing Fever Group

  • Echidna- Reptile Group

Classification:

• Bergeys Manual:

  • Phylum: Spirochaetota (or spirochetes)

  • Class: Spirochaetia

  • Order: Spirochaetales

  • Family: Borreliaceae

  • Genus: Borreila

Hierarchy:

• Domain: Bacteria

  Phylum: Spirochaetota

  Class: Spirochaetia

  Order: Spirochaetales

  Family: Borreliaceae

  Genus: Borrelia

  Species complex: B. burgdorferi sensu lato

  Species example: B. burgdorferi sensu stricto (North America)

Key Traits:

• Gram-negative spirochete

• Linear chromosome

• Low GC

Sources:

https://pmc.ncbi.nlm.nih.gov/articles/PMC8533607/

https://lpsn.dsmz.de/genus/borrelia

• Borrelia are long spiral shaped bacteria which sets them apart from other bacteria due to their unique shape.

Key Cell Structures:

• Cell Shape: Long, helical

• Cell Wall: Gram negative

• Membrane: Inner cytoplasmic membrane

• Flagella: Between inner and outer membranes which cause corkscrew motion

• Nucleoid: Linear chromosomes

• Proteins: Surface exposed lipoprotein

• Capsule: Lack capsule

Sources:

https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/borrelia-burgdorferi

https://www.mdpi.com/2079-7737/10/7/567#:~:text=Borreliae%20are%20morphologically%20characterized%20as,humans%20happening%20inadvertently%20%5B8%5D.

• Heterotroph and microaerophilic fermenter

• Uses simple sugars

• Slow growth

Growth Requirements:

• Oxygen: Microaerophilic (too much oxygen is stressful)

• Salt: Sensitive to salts and salinity

• Nutrients: Requires rich medium like rabbit serum, amino acids etc

• Temperature: Optimal growth at 32-35 degrees Celsius (similar to tick gut to human body)

• pH: Around 7.6 in unfed tick but shifts to 6.8 when fed or in host

• Other: Humidity is NEEDED

Is it a -phile?

• Technically yes, based on environmental factors.

Sources:

https://pmc.ncbi.nlm.nih.gov/articles/PMC7942402/

• Vectors

Direct or Indirect Transmission:

• No direct nor indirect transmission

Fomites:

• No role- no survival outside tick vector

Vectors:

• Ticks: Some ticks ingest Borrelia when feeding host. This goes to the ticks gut and is transferred during next feeding.

• Mechanical vectors: Not applicable for Lyme disease.

Epidemiology. Prevalence and Morbidity

• Notifiable disease:

  • Nationally notified condition since 1991

• Prevalence:

  • Estimated over 476,000 cases in US are treated and diagnosed per year

  • Annual incidence in 2022, was about 18.8 cases per 100,000 population compared to the 11.2 per 100,00 in 2017-2019.

• Morbidity

  • Death is rare, but untreated cases can lead to serious morbidity.

Outbreaks and Epidemics:

• Lyme disease is not associated with human-human contact so it doesn't spread as other diseases or sicknesses would. But it is tied to specific regions and tick populations.

Sources:

https://www.cdc.gov/lyme/data-research/facts-stats/index.html

https://www.cdc.gov/mmwr/volumes/73/wr/pdfs/mm7306a1-H.pdf

• Type: Borrelia Burgdoferi--> spirochete bacterium with linear chromosomes and multiple linear and circular plasmids in infected isolates

• Plasmids: It has a core set of plasmids

• Genome Mapped/Size: ~800 core ORFs, the linear chromosome is about ~900 kb.

Antibiotic- Resistence Genes:

• ARG presence: susceptible to most antibiotics. Most studies have have not identified significant plasmid antibiotic resistance.

Virulence Factors and Mechanisms:

• Surface lipoproteins:

  • OspC

  • OspA

  • VlsE

• Plasmid linked virulence:

  • Ip28-1

  • Ip56

Sources:

https://pmc.ncbi.nlm.nih.gov/articles/PMC10566445/

• Metabolism: microaerophilic, slow growing spirochete. Obtains energy through glycolysis

• Biochemical tests: Boriella does not typically grow on standard culture, so clinical microbiology does not work for this organism. Tests like that are not preformed

Diagnostic Tests:

• Indirect:

  • Two tiered serology:

    • 1: ELISA

    • 2: Western Blot

    • Serology is not reliable in early infection because antibodies take time to develop

• Direct:

  • PCR: Direct boriella in skin biopsy, blood samples etc BUT highly sensitive and can give false positives so not reliable.

  • Culture: Does not work

  • Antigen detection: Not enough research and not used typically.

How is it diagnosed?

• Mixture of clinical evaluation. indirect blood tests (ELISA).

Sources:

https://www.cdc.gov/lyme/diagnosis-testing/index.html

• Early localized:

  • Rash

  • Fever

  • Headache

  • Myalgia

• Early Disseminated

  • EM lesions

  • Myocarditis

  • AV block

  • Facial palsy

  • meningitis

• Late Disseminated:

  • Lyme arthritis

  • Large tissue damage

Immune Response:

• Innate Immunity and Cell Recruitment:

  • Sensors: TLR2/MyD88

    • This activates--> Monocytes and macrophages

Adaptive Immunity:

• igG antibodies: crucial for limiting tissue burdens but can't clear infection

• CD4T cells help regulate B cell responses

Autoimmunity:

• Some individuals with certain HLA alleles may be more prone to becoming autoimmune

• PTLDS: Persistent symptoms after treatment due to tissue damage.

Sources:

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