title: Polymorphisms in the nine polymorphic membrane proteins of Chlamydia trachomatis across 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.
authors.affiliation: Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
authors.forename: João P
authors.initials: JP
authors.lastname: Gomes
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nunes
authors.forename: William J
authors.initials: WJ
authors.lastname: Bruno
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Borrego
authors.forename: Carlos
authors.initials: C
authors.lastname: Florindo
authors.forename: Deborah
authors.initials: D
authors.lastname: Dean
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D002692:Chlamydia trachomatis / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity*; D052776:Female Urogenital Diseases / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D008219:Lymphogranuloma Venereum / Q000382:microbiology; D052801:Male Urogenital Diseases; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D001425:Bacterial Outer Membrane Proteins; C410161:PmpG protein, Chlamydia trachomatis