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Spirochetes

Spirochetes are helically shaped, either resembling a corkscrew or a flat wave. Spirochetes have hidden flagella and tremendous antigenic variation, making them potentially potent pathogens. Spirochetes thrive in blood, saliva and other nutrient-rich environment; they are susceptible to (and avoid via chemotaxis) H2O2 and other free radicals.

Interestingly, Borrelia species do not have LPS in their outer membranes and are neither gram-positive nor -negative. Their genome lacks any LPS biosynthesis genes. The eight genera of spirochetes are listed below. Signal transduction, motility, and chemotaxis mutants are defective in tissue penetration.

GeneraPathogenicityAssociated Diseases
Borreliaonly pathogenicLyme disease; relapsing fever; borreliosis. Life Cycle: Inoculation in the skin area.; Invasion into the bloodstream.; Leaving bloodstream and entering tissues throughout the body.
Brachyspiraparasitic or pathogenicSwine dysentery.
Brevinemaparasitic (white-footed mouse)
Cristispiraparasitic (gastropods)
Leptonemafree-living or parasitic
Leptospirafree-living parasite or pathogenLeptospirosis.
Spirochaetafree-living
Treponemaparasitic or pathogenicSyphilis; periodontitis; yaws. Life Cycle: Primary stage, Initial inoculation at genital areas and the appearance of a single sore (called a chancre); Secondary stage, The appearance of rash and mucous membrane lesions at different areas of the body, fever, fatigue, headache etc; Late Stage, Damage to internal organs, including brain, nerves, eyes, heart, blood vessels, liver, bones and joints.

Virulence factors

MotilitySpirochetes have periplasmic flagella which rotate around the cytoplasmic cylinder. Movement is rotational (snakelike) and this allows translocation in highly viscuous environments. The spirochete motility swarming assay screens fla- mutants via colony size (big colonies indicate the motile WT strain, while compact colonies indicate immotile fla- mutants). Upon isolation of fla- mutants, biochemical approaches may be used to identify which genes have been altered to induce stagnancy.
Chemotaxis

How is chemotaxisis achieved in spirochetes? They swim in presence of attracts and flex in presence of repellents. There are numerous examples of bacterial chemotaxis (enteric bacteria seek nutrients; rhizobium seek plant root; thermophiles seek heat; agrobacterium seek woundsites). However, it is less clear what spirochetes seek. Possibilities are tick salivary glands, blood, specific tissues, and immune cell evasion.

The capillary chemotaxis assay is designed to determine attracts and repellents for B. burgdorferiand and T. denticola. It is performed as follows:

  • Step 1
  • Step 2
  • Step 3
  • Step 4
  • Attractants: Serum & Saliva
  • Repellents: H2O2, and Ethanol

Flexing and swimming. The chemotactic system has 2 receptor system. The flagellar motors are special because they can go CW and CCW. Depending on the particular flagellar motor there can be coordinated or uncoordinated movement.

CheW is attached to CheA (CheW is an accessory protein acting as a coupling protein). PR methylates MCP, reducing the activity.

Pathogenic SpirochetesChemotaxis Genes
Borrelia burgdorferi2 CheA, 3 CheY, 3 CheW, 5 MCP, 1 CheX, 2 CheR
Treponema pallidum1 CheA, 1 CheY, 2 CheW, 4 MCP, 1 CheX, 1 CheR
Treponema denticola1 CheA, 1 CheY, 1 CheW, 21MCP, 1 CheX
Immune Evasion

Spirochetes evade the host immune system via motility/chemotaxis, unexposed flagella, no lipopolysaccharides, few outer membrane proteins, antigenically variable surface proteins and extracellular protease.

  • Unexposed flagellar filaments.
  • Running away from oxygen radicals.
  • Leaving bloodstream and targeting specific tissues for good hiding places.
  • Very limited surface proteins.
  • Many spirochetes (such as Borrelia) have no LPS.
  • Antigenically variable surface proteins such as Vlsproteins.
  • Multiple circular and linear plasmids with extensive recombination rates.
  • Production of extracellular proteases.
  • others

Borrelia species are neither gram-negative nor -positive, and Borrelia genome data reveals no LPS biosynthesis genes (Borellia lack LPS). The major surface proteins of pathogenic spirochetes are:

  • OspA(outer surface protein A)
  • OspB(outer surface protein B)
  • OspC(outer surface protein C)
  • OspD(outer surface protein D
  • Erps(OspErelated proteins)
  • DbpA(decorinbinding protein)
  • VlsE(Antigenicallyvariable proteins)
In Vivo Survival
ChallengeSolution
Highly viscous body fluidsCorkscrew-like movement
Numerous immune cellsNo LPS, few surface proteins, unexposed flagella, etc.
Low free iron concentrationProteins use manganese in place of iron
Abundant peptides & few carbohydratesSpirochetes degrade polypeptides for nutrition.
No cytochromes nor TCA enzymes.

Diagnosis and treatment

OspA was found in abundance by B. burgdorferi grown in laboratory medium. OspA-based Lyme vaccine was developed. Upregulated in tick larva as it becomes a nymph. Downregulated in nymph as it takes a blood meal. Not expressed on bacteria in mammal until late in infection.

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