title: The β₃-integrin ligand of Borrelia burgdorferi is critical for infection of mice but not ticks.
abstract: 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, 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 Δp66 bacteria were able to survive as well as wild type in dialysis membrane chambers in the rat peritoneum. Δp66 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 Δp66 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.
authors: Graduate Program in Microbiology, Immunology, and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: Laura C
authors: LC
authors: Ristow
authors: Halli E
authors: HE
authors: Miller
authors: Lavinia J
authors: LJ
authors: Padmore
authors: Rekha
authors: R
authors: Chettri
authors: Nita
authors: N
authors: Salzman
authors: Melissa J
authors: MJ
authors: Caimano
authors: Patricia A
authors: PA
authors: Rosa
authors: Jenifer
authors: J
authors: Coburn
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000472:pathogenicity*; D004195:Disease Models, Animal; D017353:Gene Deletion; D005816:Genetic Complementation Test; D039661:Integrin beta3 / Q000378:metabolism*; D008193:Lyme Disease / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018272:Porins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D013987:Ticks; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D039661:Integrin beta3; C107893:Oms66 protein, Borrelia; D018272:Porins; D037521:Virulence Factors