Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/135
Título: Adaptive evolution of the Chlamydia trachomatis dominant antigen reveals distinct evolutionary scenarios for B- and T-cell epitopes: worldwide survey
Autor: Nunes, A.
Nogueira, P.J.
Borrego, M.J.
Gomes, João Paulo
Palavras-chave: Infecções Sexualmente Transmissíveis
Estados de Saúde e de Doença
Determinantes da Saúde e da Doença
Data: 5-Out-2010
Editora: Public Library of Science (PLoS)
Citação: PLoS One. 2010 Oct 5;5(10). pii: e13171
Resumo: Background: Chlamydia trachomatis is one of the most disseminated human pathogens, for which no vaccine is available yet. Understanding the impact of the host pressure on pathogen antigens is crucial, but so far it was only assessed for highly-restricted geographic areas. We aimed to evaluate the evolutionary picture of the chlamydial key antigen (MOMP), which is one of the leading multi-subunit vaccine candidates, in a worldwide basis. Methodology/Principal Findings: Using genetics, molecular evolution methods and mathematical modelling, we analyzed all MOMP sequences reported worldwide, composed by 5026 strains from 33 geographic regions of five continents. Overall, 35.9% of variants were detected. The evolutionary pattern of MOMP amino acid gains/losses was found to differ from the remaining chromosome, reflecting the demanding constraints of this porin, adhesin and dominant antigen. Amino acid changes were 4.3-fold more frequent in host-interacting domains (P,10212), specifically within B-cell epitopes (P,1025), where 25% of them are at fixation (P,1025). According to the typical pathogen-host arms race, this rampant B-cell antigenic variation likely represents neutralization escape mutants, as some mutations were previously shown to abrogate neutralization of chlamydial infectivity in vitro. In contrast, T-cell clusters of diverse HLA specificities are under purifying selection, suggesting a strategy that may lead to immune subversion. Moreover, several silent mutations are at fixation, generating preferential codons that may influence expression, and may also reflect recombination-derived ‘hitchhikingeffect’ from favourable nonsilent changes. Interestingly, the most prevalent C. trachomatis genotypes, E and F, showed a mutation rate 22.3-fold lower than that of the remainder (P,10220), suggesting more fitted antigenic profiles. Conclusions/Significance: Globally, the adaptive evolution of the C. trachomatis dominant antigen is likely driven by its complex pathogenesis-related function and reflects distinct evolutionary antigenic scenarios that may benefit the pathogen, and thus should be taking into account in the development of a MOMP-based vaccine.
Peer review: yes
URI: http://hdl.handle.net/10400.18/135
ISSN: eISSN-1932-6203
Aparece nas colecções:DDI - Artigos em revistas internacionais
DEP - Artigos em revistas internacionais

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