Polymorphic Membrane Protein H Has Evolved in Parallel with the Three Disease-Causing Groups ofChlamydia trachomatis

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Abstract
Chlamydia trachomatisis a human pathogen causing trachoma, urogenital disease, and lymphogranuloma venereum (LGV). A family of nine polymorphic membrane protein genes (pmpAtopmpI), resembling autotransporter proteins, has recently been discovered inC. trachomatis. pmpgenes are large and predicted to be outer membrane proteins. We hypothesized that they would contain useful nucleotide sequence variability for epidemiologic studies. Since sequence information is available only for serovars D and L2, we sought to determine the amount of diversity within an individualpmpgene among serovars. We used restriction fragment length polymorphism (RFLP) analysis as a primary screen to assess the amount of sequence divergence among thepmpgenes for serovars A to L3 ofC. trachomatis. RFLP analysis showed little variation for some of the genes, such aspmpA, but substantial variation in others, such aspmpI. pmpHandpmpEyielded RFLP patterns that clustered the 15 serovars into ocular, urogenital, and LGV groups, and both proteins have been localized to the outer membrane. Therefore, we chose to sequencepmpE,pmpH, andpmpIfrom each of the 15 serovars. Evolutionary analysis showed three distinct divergence patterns. PmpI was least variable, resulting in an ambiguous evolutionary pattern. PmpE showed a high degree of diversity in the ocular strains compared to the other strains. Finally, the evolution of PmpH shows three groups that reflect disease groups, suggesting this protein may play a role in pathogenesis.