Disulfide-mediated oligomer formation in Borrelia burgdorferi outer surface protein C, a critical virulence factor and potential Lyme disease vaccine candidate.
Clin Vaccine Immunol
; 18(6): 901-6, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21525304
ABSTRACT
Borrelia burgdorferi OspC is an outer membrane lipoprotein required for the establishment of infection in mammals. Due to its universal distribution among B. burgdorferi sensu 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. burgdorferi B31 ospC was replaced with a C130A substitution mutant to yield strain B31ospC(C130A). Recombinant protein was also generated. Disulfide-bond-dependent oligomer formation was demonstrated and determined to be dependent on C130. Oligomerization was not required for in vivo function, as B31ospC(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 B31ospC(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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas da Membrana Bacteriana Externa
/
Vacinas contra Doença de Lyme
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Fatores de Virulência
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Dissulfetos
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Multimerização Proteica
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Antígenos de Bactérias
Limite:
Animals
Idioma:
En
Revista:
Clin Vaccine Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos