title: Delineating the requirement for the Borrelia burgdorferi virulence factor OspC in the mammalian host.
abstract: We previously demonstrated that outer surface protein C (OspC) of Borrelia burgdorferi is essential for establishing mammalian infection. However, the role of OspC in mammalian infection is unknown. Here, we report experiments designed to distinguish between two models of OspC function in the mammalian host: (i) OspC fulfills an essential physiological role for growth and host adaptation or (ii) OspC provides a protective role for evasion of components of the innate immune response. We found that a B. burgdorferi ospC mutant, previously demonstrated to be noninfectious in both immunocompetent and SCID mice, could survive in the relatively immune-privileged environment of dialysis membrane chambers implanted within the peritoneum of a rat. The ospC mutant also adapts to the mammalian environment, as determined by the protein profiles of the chamber-cultivated spirochetes. Therefore, OspC does not appear to provide a physiological function for the survival of B. burgdorferi within the mammalian host. The second model, evasion of the innate immune system, was tested by assessing the infectivity of the ospC mutant in mice deficient for myeloid differentiation protein 88 (MyD88). Recent studies have shown that B. burgdorferi is prevented from reaching high cell numbers in the mammalian host by MyD88-dependent signaling pathways. The ospC mutant was incapable of infecting MyD88-deficient mice, suggesting that the role of OspC cannot be related solely to evasion of MyD88-mediated innate immunity. These results reiterate the importance of OspC in mammalian infection and eliminate simple models of function for this enigmatic protein.
authors.affiliation: Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, NIAID, NIH, 903 South 4th St., Hamilton, MT 59840, USA. pestewart@niaid.nih.gov
authors.forename: Philip E
authors.initials: PE
authors.lastname: Stewart
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Bueschel
authors.forename: Dawn R
authors.initials: DR
authors.lastname: Clifton
authors.forename: Dorothee
authors.initials: D
authors.lastname: Grimm
authors.forename: Kit
authors.initials: K
authors.lastname: Tilly
authors.forename: James A
authors.initials: JA
authors.lastname: Carroll
authors.forename: Janis J
authors.initials: JJ
authors.lastname: Weis
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Rosa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D025065:Borrelia burgdorferi / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D007113:Immunity, Innate; D008193:Lyme Disease / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88; D010537:Peritoneum / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D037521:Virulence Factors / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C507780:Myd88 protein, mouse; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; C079616:OspC protein; D037521:Virulence Factors