Disulfide-Mediated Oligomer Formation in Borrelia burgdorferi Outer Surface Protein C, a Critical Virulence Factor and Potential Lyme Disease Vaccine Candidate
| Autor: | Christopher G. Earnhart, DeLacy V. L. Rhodes, Richard T. Marconi |
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| Rok vydání: | 2011 |
| Předmět: |
Microbiology (medical)
Antigenicity Virulence Factors Clinical Biochemistry Immunology Mutagenesis (molecular biology technique) Immunoglobulin G Virulence factor Microbiology Mice Borrelia burgdorferi Group Animals Immunology and Allergy Cysteine Disulfides Borrelia burgdorferi Infectivity Antigens Bacterial Mice Inbred C3H biology Lyme Disease Vaccines Vaccine Research bacterial infections and mycoses biology.organism_classification Antibodies Bacterial Virology Isotype Amino Acid Substitution Mutagenesis Site-Directed biology.protein Protein Multimerization Bacterial outer membrane Bacterial Outer Membrane Proteins |
| Zdroj: | Clinical and Vaccine Immunology. 18:901-906 |
| ISSN: | 1556-679X 1556-6811 |
| Popis: | Borrelia burgdorferiOspC is an outer membrane lipoprotein required for the establishment of infection in mammals. Due to its universal distribution amongB. burgdorferisensu lato strains and high antigenicity, it is being explored for the development of a next-generation Lyme disease vaccine. An understanding of the surface presentation of OspC will facilitate efforts to maximize its potential as a vaccine candidate. OspC forms homodimers at the cell surface, and it has been hypothesized that it may also form oligomeric arrays. Here, we employ site-directed mutagenesis to test the hypothesis that interdimeric disulfide bonds at cysteine 130 (C130) mediate oligomerization.B. burgdorferiB31ospCwas replaced with a C130A substitution mutant to yield strain B31::ospC(C130A). Recombinant protein was also generated. Disulfide-bond-dependent oligomer formation was demonstrated and determined to be dependent on C130. Oligomerization was not required forin vivofunction, as B31::ospC(C130A) retained infectivity and disseminated normally. The total IgG response and the induced isotype pattern were similar between mice infected with untransformed B31 and those infected with the B31::ospC(C130A) strain. These data indicate that the immune response to OspC is not significantly altered by formation of OspC oligomers, a finding that has significant implications in Lyme disease vaccine design. |
| Databáze: | OpenAIRE |
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