Delineating the Requirement for theBorrelia burgdorferiVirulence Factor OspC in the Mammalian Host
- 1 June 2006
- journal article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 74 (6), 3547-3553
- https://doi.org/10.1128/iai.00158-06
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.Keywords
This publication has 58 references indexed in Scilit:
- Borrelia burgdorferi OspC Protein Required Exclusively in a Crucial Early Stage of Mammalian InfectionInfection and Immunity, 2006
- The Lyme disease agent exploits a tick protein to infect the mammalian hostNature, 2005
- Relative Contributions of Innate and Acquired Host Responses to Bacterial Control and Arthritis Development in Lyme DiseaseInfection and Immunity, 2005
- Toll-like receptor signallingNature Reviews Immunology, 2004
- Immune evasion of Borrelia burgdorferi: mapping of a complement‐inhibitor factor H‐binding site of BbCRASP‐3, a novel member of the Erp protein familyEuropean Journal of Immunology, 2003
- Clonal Polymorphism of Borrelia burgdorferi Strain B31 MI: Implications for Mutagenesis in an Infectious Strain BackgroundInfection and Immunity, 2002
- Host Defense Mechanisms Triggered by Microbial Lipoproteins Through Toll-Like ReceptorsScience, 1999
- A new animal model for studying Lyme disease spirochetes in a mammalian host-adapted state.JCI Insight, 1998
- High-resolution Structures of the Ligand Binding Domain of the Wild-type Bacterial Aspartate ReceptorJournal of Molecular Biology, 1996
- Nucleotide sequence and analysis of the gene inBorrelia burgdorferiencoding the immunogenic P39 antigenFEMS Microbiology Letters, 1994