Polymorphisms in the Nine Polymorphic Membrane Proteins of Chlamydia trachomatis across All Serovars: Evidence for Serovar Da Recombination and Correlation with Tissue Tropism

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 orderChlamydiales . Genomic and molecular analyses were performed for the entirepmp 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% forpmpA to 7.0% forpmpF . Lymphogranuloma venereum (LGV) serovars were the most closely related for thepmp genes and were also the most divergent, compared to ocular and non-LGV urogenital disease groups. Phylogenetic reconstructions showed that for six of ninepmp genes (notpmpA ,pmpD , orpmpE ), the serovars clustered based on tissue tropism. The most globally successful serovars, E and F, clustered distantly from the urogenital group for fivepmp genes. Thesepmp genes may confer a biologic advantage that may facilitate infection and transmission for E and F. Surprisingly, serovar Da clustered with the ocular group frompmpE topmpI , 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 forpmpE ,pmpF , andpmpH where substitutions were concentrated and associated with a specific disease group. Thus, our data suggest a possible structural or functional role that may vary amongpmp genes in promoting antigenic polymorphisms and/or diverse adhesions-receptors that may be involved in immune evasion and differential tissue tropism.