Autor(es):
Nunes, A. 
; Nogueira, P.J. ; Borrego, M.J. ; Gomes, J.P.
Data: 2010
Identificador Persistente: http://hdl.handle.net/10400.18/135
Origem: Repositório Científico do Instituto Nacional de Saúde
Assunto(s): Infecções Sexualmente Transmissíveis; Estados de Saúde e de Doença; Determinantes da Saúde e da Doença
Descrição
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.
