Faculty Collaboration Database

Integrin binding by Borrelia burgdorferi P66 facilitates dissemination but is not required for infectivity. Cell Microbiol 2015 Jul;17(7):1021-36 PMID: 25604835 PMCID: PMC4478124

Pubmed ID

25604835

DOI

10.1111/cmi.12418

Abstract

P66, a Borrelia burgdorferi surface protein with porin and integrin-binding activities, is essential for murine infection. The role of P66 integrin-binding activity in B. burgdorferi infection was investigated and found to affect transendothelial migration. The role of integrin binding, specifically, was tested by mutation of two amino acids (D205A,D207A) or deletion of seven amino acids (Del202-208). Neither change affected surface localization or channel-forming activity of P66, but both significantly reduced binding to αv β3 . Integrin-binding deficient B. burgdorferi strains caused disseminated infection in mice at 4 weeks post-subcutaneous inoculation, but bacterial burdens were significantly reduced in some tissues. Following intravenous inoculation, the Del202-208 bacteria were below the limit of detection in all tissues assessed at 2 weeks post-inoculation, but bacterial burdens recovered to wild-type levels at 4 weeks post-inoculation. The delay in tissue colonization correlated with reduced migration of the Del202-208 strains across microvascular endothelial cells, similar to Δp66 bacteria. These results indicate that integrin binding by P66 is important to efficient dissemination of B. burgdorferi, which is critical to its ability to cause disease manifestations in incidental hosts and to its maintenance in the enzootic cycle.

Author List

Ristow LC, Bonde M, Lin YP, Sato H, Curtis M, Wesley E, Hahn BL, Fang J, Wilcox DA, Leong JM, Bergström S, Coburn J

Authors

Jenifer Coburn PhD Professor in the Medicine department at Medical College of Wisconsin
David A. Wilcox PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

Scopus

2-s2.0-84931571353   16 Citations

MESH terms used to index this publication - Major topics in bold

Amino Acid Substitution
Animals
Bacterial Adhesion
Bacterial Load
Bacterial Proteins
Borrelia burgdorferi
Cell Line
Endothelial Cells
Host-Pathogen Interactions
Humans
Integrin alphaVbeta3
Mice, Inbred C3H
Mutant Proteins
Porins
Protein Binding
Sequence Deletion