title: Integrin binding by Borrelia burgdorferi P66 facilitates dissemination but is not required for infectivity.
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.
authors.affiliation: Graduate Program in Microbiology, Immunology, and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.|Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Ristow
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden.
authors.forename: Mari
authors.initials: M
authors.lastname: Bonde
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Yi-Pin
authors.initials: YP
authors.lastname: Lin
authors.affiliation: Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, WI, USA.|Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Graduate Program in Microbiology, Immunology, and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.|Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Curtis
authors.affiliation: Graduate Program in Microbiology, Immunology, and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Wesley
authors.affiliation: Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, WI, USA.|Division of Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Hahn
authors.affiliation: Department of Pediatrics, MACC Fund Research Center, Children's Research Institute, Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Pediatrics, MACC Fund Research Center, Children's Research Institute, Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wilcox
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Leong
authors.affiliation: Department of Molecular Biology, Umeå University, Umeå, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Bergström
authors.affiliation: Graduate Program in Microbiology, Immunology, and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI, USA.|Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, WI, USA.|Division of Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Coburn
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001422:Bacterial Adhesion; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000502:physiology*; D002460:Cell Line; D042783:Endothelial Cells / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008809:Mice, Inbred C3H; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D018272:Porins / Q000378:metabolism*; D011485:Protein Binding; D017384:Sequence Deletion
chemical_list: D001426:Bacterial Proteins; D039302:Integrin alphaVbeta3; D050505:Mutant Proteins; C107893:Oms66 protein, Borrelia; D018272:Porins