Polymorphisms in the Nine Polymorphic Membrane Proteins ofChlamydia trachomatisacross All Serovars: Evidence for Serovar Da Recombination and Correlation with Tissue Tropism

Abstract

Chlamydia trachomatis is an intracellular bacterium responsible for ocular, respiratory, and sexually transmitted diseases. The genome contains a nine-member polymorphic membrane protein (Pmp) family unique to members of the order Chlamydiales. Genomic and molecular analyses were performed for the entire pmp gene family for the 18 reference serological variants (serovars) and genovariant Ja to identify specific gene and protein regions that differentiate chlamydial disease groups. The mean genetic distance among all serovars varied from 0.1% for pmpA to 7.0% for pmpF. Lymphogranuloma venereum (LGV) serovars were the most closely related for the pmp genes and were also the most divergent, compared to ocular and non-LGV urogenital disease groups. Phylogenetic reconstructions showed that for six of nine pmp genes (not pmpA, pmpD, or pmpE), the serovars clustered based on tissue tropism. The most globally successful serovars, E and F, clustered distantly from the urogenital group for five pmp genes. These pmp genes may confer a biologic advantage that may facilitate infection and transmission for E and F. Surprisingly, serovar Da clustered with the ocular group from pmpE to pmpI, which are located together in the chromosome, providing statistically significant evidence for intergenomic recombination and acquisition of a genetic composition that could hypothetically expand the host cell range of serovar Da. We also identified distinct domains for pmpE, pmpF, and pmpH where substitutions were concentrated and associated with a specific disease group. Thus, our data suggest a possible structural or functional role that may vary among pmp genes in promoting antigenic polymorphisms and/or diverse adhesions-receptors that may be involved in immune evasion and differential tissue tropism.

Immunoproteomic Discovery of Novel T Cell Antigens from the Obligate Intracellular PathogenChlamydia

“…The authors concluded that Chlamydia PmpF could be a particularly important immune target of T cells and that variability in the MHC-binding epitopes of PmpF could help the pathogen evade host immune responses. This speculation is further supported by the finding that PmpF is the most polymorphic protein among all C. trachomatis Pmps (39). The identification of PmpE/ F-2-derived peptide in this study could be explained by its possible unique role in MHC peptide binding and/or by its abundance because pmpF also has the highest mRNA expression level among tested C. trachomatis strains (40).…”

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen

“…The widespread recombination observed between ompA alleles also explains why ompA-based strain typing in some cases correlates poorly with the clinical phenotypes and infection site tropisms of C. trachomatis serovars. Furthermore, typing of loci from highly variable regions of the genome, such as the plasticity zone and the polymorphic membrane protein (pmp) genes, as well as multilocus sequencing typing (MLST), further supports the notion that recombination extends beyond the ompA locus and is pervasive throughout the C. trachomatis genome (116)(117)(118)(119)(120)(121).…”

Polymorphisms in Inc Proteins and Differential Expression ofincGenes among Chlamydia trachomatis Strains Correlate with Invasiveness and Tropism of Lymphogranuloma Venereum Isolates

“…Therefore, the determinants of the different types of infection (invasive or noninvasive) and tissue tropism (eyes, genitals, and lymph nodes) must rely on the few genes present in some strains but not in others and on nucleotide differences which may lead either to proteins with disease group-specific amino acids or to differential gene expression. Some of these determinants were suggested in previous studies: the tryptophan (trpRBA) operon (10,19,51) and genes encoding cytotoxin (11), phospholipase (40), polymorphic membrane proteins (Pmps) (24), and Tarp (34).…”

“…PCR products were purified after agarose gel electrophoresis, using a High Pure PCR purification kit (Roche), and then subjected to DNA sequencing. To analyze the determined TSSs in the context of the promoter regions of ct059-ct058, ct192, and ct214 in all strains used in the RT-qPCR assays, the corresponding nucleotide sequences were either retrieved from GenBank (E/Bour, L2/434, and L3/ 404; see Table S1 in the supplemental material) or determined by DNA sequencing (C/TW3, B/Har36, F/CS465-95, and L2b/CS19-08), as previously described (24) and using the primers listed in Table S2. All these manipulations were done according to instructions from the indicated manufacturers.…”

“…For the analyses of polymorphism, phylogeny, and molecular evolution, various tools present in MEGA5 were used, essentially as previously described (24). Briefly, for analyses of polymorphism, we computed pairwise, overall, within-group (ocular, urogenital, or LGV), and betweengroup (ocular versus urogenital, ocular versus LGV, or urogenital versus LGV) amino acid p distances.…”