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The ??-integrin ligand of Borrelia burgdorferi is critical for infection of mice but not ticks.

ABSTRACT: P66 is a Borrelia burgdorferi surface protein with ?? integrin binding and channel forming activities. In this study, the role of P66 in mammalian and tick infection was examined. B.?burgdorferi?p66 strains were not infectious in wild-type, TLR2?/?- or MyD88?/?-deficient mice. Strains with p66 restored to the chromosome restored near wild-type infectivity, while complementation with p66 on a shuttle vector did not restore infectivity. ?p66 mutants are cleared quickly from the site of inoculation, but analyses of cytokine expression and cellular infiltrates at the site of inoculation did not reveal a specific mechanism of clearance. The defect in these mutants cannot be attributed to nutrient limitation or an inability to adapt to the host environment in vivo as ?p66 bacteria were able to survive as well as wild type in dialysis membrane chambers in the rat peritoneum. ?p66 bacteria were able to survive in ticks through the larva to nymph moult, but were non-infectious in mice when delivered by tick bite. Independent lines of evidence do not support any increased susceptibility of the ?p66 strains to factors in mammalian blood. This study is the first to define a B.?burgdorferi adhesin as essential for mammalian, but not tick infection.

SUBMITTER: Ristow LC

PROVIDER: S-EPMC3438374 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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The β₃-integrin ligand of Borrelia burgdorferi is critical for infection of mice but not ticks.

Ristow Laura C LC Miller Halli E HE Padmore Lavinia J LJ Chettri Rekha R Salzman Nita N Caimano Melissa J MJ Rosa Patricia A PA Coburn Jenifer J

Molecular microbiology 20120718 6

P66 is a Borrelia burgdorferi surface protein with β₃ integrin binding and channel forming activities. In this study, the role of P66 in mammalian and tick infection was examined. B. burgdorferiΔp66 strains were not infectious in wild-type, TLR2⁻/⁻- or MyD88⁻/⁻-deficient mice. Strains with p66 restored to the chromosome restored near wild-type infectivity, while complementation with p66 on a shuttle vector did not restore infectivity. Δp66 mutants are cleared quickly from the site of inoculation ...[more]

PMID: 22758390

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Project description:Lyme disease is a major vector-borne bacterial disease in the USA. The disease is caused by Borrelia burgdorferi, and transmitted among hosts and humans, primarily by blacklegged ticks (Ixodes scapularis). The ~25 B. burgdorferi genotypes, based on genotypic variation of their outer surface protein C (ospC), can be phenotypically separated as strains that primarily cause human diseases-human invasive strains (HIS)-or those that rarely do. Additionally, the genotypes are non-randomly associated with host species. The goal of this study was to examine the extent to which phenotypic outcomes of B. burgdorferi could be explained by the host communities fed upon by blacklegged ticks. In 2006 and 2009, we determined the host community composition based on abundance estimates of the vertebrate hosts, and collected host-seeking nymphal ticks in 2007 and 2010 to determine the ospC genotypes within infected ticks. We regressed instances of B. burgdorferi phenotypes on site-specific characteristics of host communities by constructing Bayesian hierarchical models that properly handled missing data. The models provided quantitative support for the relevance of host composition on Lyme disease risk pertaining to B. burgdorferi prevalence (i.e. overall nymphal infection prevalence, or NIPAll) and HIS prevalence among the infected ticks (NIPHIS). In each year, NIPAll and NIPHIS was found to be associated with host relative abundances and diversity. For mice and chipmunks, the association with NIPAll was positive, but tended to be negative with NIPHIS in both years. However, the direction of association between shrew relative abundance with NIPAll or NIPHIS differed across the two years. And, diversity (H') had a negative association with NIPAll, but positive association with NIPHIS in both years. Our analyses highlight that the relationships between the relative abundances of three primary hosts and the community diversity with NIPAll, and NIPHIS, are variable in time and space, and that disease risk inference, based on the role of host community, changes when we examine risk overall or at the phenotypic level. Our discussion focuses on the observed relationships between prevalence and host community characteristics and how they substantiate the ecological understanding of phenotypic Lyme disease risk.

Dataset Information

The ??-integrin ligand of Borrelia burgdorferi is critical for infection of mice but not ticks.

Publications

The β₃-integrin ligand of Borrelia burgdorferi is critical for infection of mice but not ticks.

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