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

Abstract

Chlamydia trachomatis is a human pathogen causing trachoma, urogenital disease, and lymphogranuloma venereum (LGV). A family of nine polymorphic membrane protein genes (pmpA to pmpI), resembling autotransporter proteins, has recently been discovered in C. trachomatis. pmp genes 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 individual pmp gene among serovars. We used restriction fragment length polymorphism (RFLP) analysis as a primary screen to assess the amount of sequence divergence among the pmp genes for serovars A to L3 of C. trachomatis. RFLP analysis showed little variation for some of the genes, such as pmpA, but substantial variation in others, such as pmpI. pmpH and pmpE yielded 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 sequence pmpE, pmpH, and pmpI from 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.

Recombination in the Genome ofChlamydia trachomatisInvolving the Polymorphic Membrane Protein C Gene Relative toompAand Evidence for Horizontal Gene Transfer

“…We also found that serovars Da, E, and F evolved separately from the other urogenital serovars, as evidenced by a distant phylogenetic branch from the urogenital group. A similar branch was observed for pmpI (47). This is interesting, because serovars E, F, and D/Da are the most prevalent serovars among sexually transmitted disease populations worldwide.…”

“…The pmpC tree revealed a separate clade that clearly distinguishes LGV serovars from all others, as was the case for pmpH. Also, ocular serovars were clustered together for pmpC, although this is more evident for pmpE and pmpH (47). We also found that serovars Da, E, and F evolved separately from the other urogenital serovars, as evidenced by a distant phylogenetic branch from the urogenital group.…”

“…Data regarding the pmpC phylogenetic trees obtained by this method were compared with the available data in the literature for other C. trachomatis genes (14,32,47).…”

The AlternativeTranslational Profile That Underlies the Immune-Evasive State of Persistence in Chlamydiaceae Exploits Differential Tryptophan Contents of the Protein Repertoire

“…However, other serovars cause ocular trachoma or lymphogranuloma venereum. In a study that included 15 serovars representing these three disease groups, it is interesting that the PmpH family produced a tripartite tree that exactly paralleled the disease group into which a given serovar fell (123).…”

Type V Protein Secretion Pathway: the Autotransporter Story

“…The recent completion of five chlamydial genome sequences has led to the division of the Chlamydiaceae into two genera; Chlamydia (Chlamydia trachomatis, Chlamydia suis, and Chlamydia muridarum), and Chlamydophila (Chlamydophila pneumoniae, Chlamydophila abortus, Chlamydophila psittaci, Chlamydophila pecorum, Chlamydophila felis, and Chlamydophila caviae) (77,126). However, despite these phylogenetic differences, all the species demonstrate commonalities in their life cycles, virulence traits, and modes of host and tissue tropism (77,186,469). Indeed, all members of the Chlamydiaceae possess a developmental life cycle that alternates between the infectious extracellular form termed the elementary body (EB) and the metabolically active form termed the reticulate body (RB); the EB develops into the RB after infection (186).…”