Chlamydia trachomatis is the
trachoma agent and causes most
bacterial sexually transmitted infections worldwide. Its major outer
membrane protein (MOMP) is a well-known
porin and
adhesin and is the dominant
antigen. So far, investigation of MOMP variability has been focused mainly on molecular
epidemiological surveys. In contrast, we aimed to evaluate the impact of the host pressure on this key
antigen by analyzing its evolutionary dynamics in 795 isolates from
urogenital infections, taking into account the MOMP
secondary structure and the sizes/positions of
antigenic regions. One-third of the specimens showed a mutational drift from the corresponding
genotype, where approximately 42% of the
mutations had never been described.
Amino acid alterations were sixfold more frequent within
B-cell epitopes than in the remaining protein (P = 0.027), and some
mutations were also found within or close to
T-cell antigenic clusters. Interestingly, the two most ecologically successful
genotypes, E and F, showed a
mutation rate 60.3-fold lower than that of the other
genotypes (P < 10(-8)), suggesting that their efficacy may be the result of a better fitness in dealing with the host
immune system rather than of specific
virulence factors. Furthermore, the variability exhibited by some
genetic variants involved residues that are known to play a critical role during the membrane mechanical movements, contributing to a more stable and flexible
porin conformation, which suggests some plasticity to deal with environmental pressure. Globally, these MOMP mutational trends yielded no mosaic structures or important
phylogenetic changes, but instead yielded
point mutations on specific
protein domains, which may enhance pathogen's
infectivity, persistence, and transmission.
