Chlamydia trachomatis-Infected Patients Display Variable Antibody Profiles against the Nine-Member Polymorphic Membrane Protein Family

Abstract

Genomic analysis of the Chlamydiaceae has revealed a multigene family encoding large, putatively autotransported polymorphic membrane proteins (Pmps) with nine members in the sexually transmitted pathogen Chlamydia trachomatis. While various pathogenesis-related functions are emerging for the Pmps, observed genotypic and phenotypic variation among several chlamydial Pmps in various Chlamydia species has led us to hypothesize that the pmp gene repertoire is the basis of a previously undetected mechanism of antigenic variation. To test this hypothesis, we chose to examine the serologic response of C. trachomatis-infected patients to each Pmp subtype. Immune serum samples were collected from four populations of patients with confirmed C. trachomatis genital infection: 40 women with pelvic inflammatory disease from Pittsburgh, PA; 27 and 34 adolescent/young females from Oakland, CA, and Little Rock, AR, respectively; and 58 adult male patients from Baltimore, MD. The Pmp-specific antibody response was obtained using immunoblot analysis against each of the nine recombinantly expressed Pmps and quantified by densitometry. Our results show that nearly all C. trachomatis-infected patients mount a strong serologic response against individual or multiple Pmp subtypes and that the antibody specificity profile varies between patients. Moreover, our analysis reveals differences in the strengths and specificities of the Pmp subtype-specific antibody reactivity relating to gender and clinical outcome. Overall, our results indicate that the Pmps elicit various serologic responses in C. trachomatis-infected patients and are consistent with the pmp gene family being the basis of a mechanism of antigenic variation.

Directional Evolution of Chlamydia trachomatis towards Niche-Specific Adaptation

“…These include genes encoding two polymorphic membrane proteins (Pmps) (CT869/pmpE and CT870/pmpF), one Pmp-like protein (CT050), one inclusion membrane protein (Inc) (CT115/incD), and the translocated actin recruiting phosphoprotein (CT456/tarp). The Pmps and Incs are among the most promising research targets for which there is cumulative evidence of their involvement in biological mechanisms, such as adhesion, immune response elicitation, or subversion of intracellular trafficking (see Table 1 for details) (21,25,35,38,66,68,78). For example, PmpF was predicted in silico to contain T-cell epitopes that bind HLA class I and II alleles (15).…”

A characteristic of polymorphic membrane protein F of Chlamydia trachomatis isolated from male urogenital tracts in Japan

“…In contrast to the β-barrel domain, the PmpF passenger domains have been shown to undergone amino acid changes throughout evolution because of surface localization [13][14][15]. Thus, polymorphism of the PmpF passage domain, which is exposed to strong host-selective pressures, has been thought to be a candidate high-definition phylogenetic marker [8][9][10][11][12][13]. The Japan-female strains isolated from cervical ducts with microbial flora were very diverse in agreement with the Ref-females as well as previous findings [12,13].…”

“…Thus, polymorphism of the PmpF passage domain, which is exposed to strong host-selective pressures, has been thought to be a candidate high-definition phylogenetic marker [8][9][10][11][12][13]. The Japan-female strains isolated from cervical ducts with microbial flora were very diverse in agreement with the Ref-females as well as previous findings [12,13]. Correspondingly, the homosexual male PmpFs of C. trachomatis strains isolated from rectum with microbial flora were similarly in diverse as well as female PmpFs, supporting our hypothesis.…”

“…To date, most studies of C. trachomatis bacterial traits have focused on strains isolated from women, whereas the study of bacteria from the male urogenital tract has been hindered by difficulties in the isolation of organisms. Meanwhile, accumulating evidences have revealed a high-definition phylogenetic marker, polymorphic membrane protein (Pmp), which diversifies into nine Pmp families (A-I) in C. trachomatis [8][9][10][11][12][13].…”

Development of a chlamydial vaccine for koalas (Phascolarctos cinereus)

“…Pmps play critical roles in chlamydial biology and virulence [156,157], as they represent 13.6% and 17.5% of the coding capacity of these two genomes, It is suggested that these diversified proteins play vital roles in escaping from host immune surveillance [158,159]. The pmp genes are predicted to encode membrane proteins to be localized in the outer membrane, due to the tryptophan residues in the C-terminal half and a C-terminal phenylalanine residue [160][161][162][163].…”