Borelia burgdorferi and Lyme disease

• What are the spriochaetota?

  This is a phylum of bacteria, which contains distinctive gram negative bacteria which exhibit a helically coiled cells.
• Describe how B. Burgdorferi exhibits a helical structure

  The helical shape is imparted by the periplasmic flagella. The flagella insertion points are located near the termini of the spirochaete and bundles of flagella wind around the flexible rod shaped protoplasmic cylinder to over lap in the middle. The outer membrane constrains the flagella’s bundles within the periplasm.
• Describe the symptoms of Lyme disease infection

  • Ticks can transmit bacteria during feedinG
  • Systemic infection- headache, chills, fatigue and rash
  • Tick becomes partially engorged and a ”bulls eye’ rash forms, which develops into a circular rash
  • Treatable with antibiotics
  • Untreated disease will progress over weeks to chronic stage-
  • arthritis and neurological symptoms
  • heart damage and limb weakness
• Describe the course of B. burgdorferi infection and Lyme disease in humans

  1. Bacteria begin to multiple and altered gene expression allows them to disseminate from the tick
  2. The bacteria are then inoculated into the skin and spread within the skin, leading to rash formation.
  3. Bacteria can then invade the blood vessels to spread to other tissues (systemic infection)
  4. Persistent infection of multiple tissues, including joints, CNS, PNS and skin.
  5. Continued multiplication and invasion of multiple tissue sites leads to non-specific illness.
• Describe the genomics of Borellia Burgdorferi

  • Complex 1 Mbp linear chromosome- contains relatively conserved genes
  • Large number of linear and circular plasmids, totalling around 600 kb- contains less conserved genes
  • Linear replicons terminate with covalently closed hairpins that require telomere resolvase for replication
  • Recent evidence suggests that cells are polyploid with multiple copies of chromosome and plasmids along the cell length
• Describe how Borellia is autotrophic

  • Due to its parasitic lifestyle, Borellia has lost many metabolic activities
  • does not require iron, which is replaced with manganese metalloproteins
  • auxotrophic for all amino acids, nucleotides and fatty acids
  • No TCA cycle of oxidative phosphorylation, instead acquires energy from fermentation of sugars via Embden-Meyerhof pathway
• Describe the cell surface of Borellia

  • Lack LPS within their outer membrane
  • instead it is composed of lipids, Phosphatidylcholine, Phosphatidylglycerol and cholesterol.
  • Few proteins with membrane spanning domains
  • Key property is the presence of many lipoproteins
  • OSPs- outer surface proteins, which are differentially expressed during infection (see image)

  
• Describe the differential gene expression of B. burgdorferi Lyme disease

  • Tick gut- B. burgdorferi upregulates ospA gene expression, which binds to the tick receptor for OspA (TROSPA). Allows the bacteria to attach.
  • TIck feeding- B. burgdorferi switches off ospA gene expression and upregulates ospC production and migrates to the salivary gland. OspC binds to tick salivary protein, Salp15, which is an immunosuppressant.
• Describe the action of Salp15

  This is an immunosuppressant that inhibits CD4+ T cell activation, by preventing the interaction between antigen presenting cells and TCR on T-cells. Also protects against antibody mediated killing, by shielding B. burgdorferi from antibody action.
• Describe antigenic diversity of B. burgdorferi

  • VlsE is a lipoprotein expressed from the linear plasmid and located near the telomere
  • VlsE shields Borellia cell surface proteins from antibody action
  • Recombination events lead to alteration of the variable regions by variable donor sections to generate new sequences. This is a mechanism to generate antigenic diversity, allowing Borellia to evade host adaptive immune response.
  • Mutants lack VlsE do not persist and are cleared from mice
• Describe the life cycle of ticks and how this relates to transmission of B. burgdorferi

  1. Eggs hatch into spirochaete free larvae, so no transovarial transmission from adult to egg.
  2. Larvae feed on small animals such as mice and acquire B. burgdorferi from infected reservoir animals. Borellia is retained during subsequent stages as the larvae becomes a nymph.
  3. Nymphs feed on a range of hosts and can transmit spirochaetes to a new reservoir of hosts, such as humans.
  4. most common mode of transmission to humans
  5. Adult tickets feed on larger animals such as deer and humans.