Adaptive Evolution of the Chlamydia trachomatis Dominant Antigen Reveals Distinct Evolutionary Scenarios for B- and T-cell Epitopes: Worldwide Survey
نویسندگان
چکیده
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<10⁻¹²), specifically within B-cell epitopes (P<10⁻⁵), where 25% of them are at fixation (P<10⁻⁵). 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 'hitchhiking-effect' 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<10⁻²⁰), 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.
منابع مشابه
B and T-Cell Epitope Prediction of the OMP25 Antigen for Developing Brucella melitensis Vaccines for Sheep
Brucellosis, produced by Brucella species, is a disease that causes severe economic losses for livestock farms worldwide Due to serious economic and medical consequences of this disease, many efforts have been made to prevent the infection through the use of recombinant vaccines based on Brucella outer membrane protein (OMP) antigens. In the present study, a wide range of on-line prediction sof...
متن کاملIn Silico Prediction of B-Cell and T-Cell Epitopes of Protective Antigen of Bacillus anthracis in Development of Vaccines Against Anthrax
Protective antigen (PA), a subunit of anthrax toxin from Bacillus anthracis, is known as a dominant component in subunit vaccines in protection against anthrax. In order to avoid the side effects of live attenuated and killed organisms, the use of linear neutralizing epitopes of PA is recommended in order to design recombinant vaccines. The present study is aimed at determining the dominant epi...
متن کاملP-59: Chlamydia Trachomatis Infection in Femaleswith Secondary Infertility
Background: We designed a prospective study to assess the role of Chlamydia in secondary infertility Materials and Methods: 40 women with secondary infertility and 30 term healthy pregnant women of similar age composition were studied for past and present chlamydia trachomatis infection. Women attending the outpatient department of Obstetrics and Gynaecology with complaint of secondary infertil...
متن کاملPrevalence of Chlamydia trachomatis Antigen and Antibody in Infertile Women in Ahwaz
Chlamydia trachomatis is an obligate intracellular bacterium which causes a wide variety of human infections such as ocular, urogenital and respiratory infections. Genital infections of women, espe-cially when repeated, give rise to many complications such as ectopic pregnancy, miscarriage and infertility. Since chlamydial infections are usually asymptomatic, they progress unnoticed and produc...
متن کاملIdentification of Two Epitopes on the Outer Surface Protein A of the Lyme Disease Spirochete Borrelia burgdorferi
A murine IgM monoclonal antibody (MA-2C6) with κ-light chains directed against an antigenic determinant of outer surface protein A (OspA) of the Lyme disease spirochete, Borreliaburgdorferi, is produced. This antibody could bind specifically to OspA antigen of several isolates of B. burgdorferi, but not to the non-Lyme disease bacteria such as T. pallidum and B. hermsii. Antibody MA-2C6 was pur...
متن کامل