The β₃-integrin ligand of Borrelia burgdorferi is critical for infection of mice but not ticks. Mol Microbiol 2012 Sep;85(6):1105-18
Date
07/05/2012Pubmed ID
22758390Pubmed Central ID
PMC3438374DOI
10.1111/j.1365-2958.2012.08160.xScopus ID
2-s2.0-84866024708 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
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.
Author List
Ristow LC, Miller HE, Padmore LJ, Chettri R, Salzman N, Caimano MJ, Rosa PA, Coburn JAuthors
Jenifer Coburn PhD Professor in the Medicine department at Medical College of WisconsinNita H. Salzman MD, PhD Center Director, Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBacterial Adhesion
Bacterial Proteins
Borrelia burgdorferi
Disease Models, Animal
Gene Deletion
Genetic Complementation Test
Integrin beta3
Lyme Disease
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Porins
Protein Binding
Rats
Ticks
Virulence
Virulence Factors
