Altered developmental expression of polymorphic membrane proteins in penicillin-stressed Chlamydia trachomatis

Abstract

Late C. trachomatis inclusions express each member of the surface-exposed polymorphic membrane protein family (Pmp subtypes A through I) with a reproducible distribution of fully-on, fully-off and intermediate phenotypes. This observation is consistent with observed variable Pmp antibody profiles in C. trachomatis-infected patients and has led to the hypothesis that the pmp gene family forms the basis of a phase variation-like mechanism of antigenic variation. Here we investigate and compare the developmental expression of each of the nine pmp genes under conditions of optimal in vitro growth with that under conditions that promote prolonged survival of chlamydiae when exposed to penicillin-induced stress. We demonstrate that the pmp gene family includes distinct transcriptional units that are differentially expressed along development and differentially responsive to stress. In particular, our results indicate that expression of pmpA, pmpD and pmpI is uniquely unaffected by stress, suggesting that the PmpA, PmpD and PmpI proteins play a critical role in the pathogenesis of C. trachomatis.

Reversible Inhibition of Chlamydia trachomatis Infection in Epithelial Cells Due to Stimulation of P2X 4 Receptors

“…These data suggest that C. trachomatis remains viable within host cells for extended times following extracellular ADP or ATP stimulation and are able to reengage their developmental program when growth conditions are no longer prohibitive. Reversible inhibition of chlamydial infection through P2X 4 ligation thus resembles responses previously described for persistence of chlamydial infection (4,15,43,53). …”

Chlamydial polymorphic membrane proteins: regulation, function and potential vaccine candidates

“…28 Furthermore, pmpABC, pmpFE and pmpGH are co-transcribed in vitro indicating that these genes are organized in operons. 54 Of all of the C. trachomatis Pmps, PmpA, D and I are the most conserved, with PmpA having 99.9%, PmpD 99.1% and PmpI 99.2% amino acid sequence similarity. 54 All 9 pmps have been shown to be transcribed in vitro in various C. trachomatis strains including serovars D, E, and L2 17,31,55 and are all translocated to the bacterial surface.…”

“…54 Of all of the C. trachomatis Pmps, PmpA, D and I are the most conserved, with PmpA having 99.9%, PmpD 99.1% and PmpI 99.2% amino acid sequence similarity. 54 All 9 pmps have been shown to be transcribed in vitro in various C. trachomatis strains including serovars D, E, and L2 17,31,55 and are all translocated to the bacterial surface. 17 However, C. trachomatis pmp paralogues exhibit variable transcription patterns.…”

Identification of Antigen-Specific Antibody Responses Associated with Upper Genital Tract Pathology in Mice Infected with Chlamydia muridarum

“…After replication, the progeny RBs differentiate back into EBs to spread to nearby cells. At the individual organism level, the biphasic developmental cycle is highly asynchronous, and protein expression profiles also vary considerably (11), which may contribute to the chlamydial ability to deal with varied host environments and defense mechanisms. However, it has been difficult to directly detect chlamydial protein expression during natural infection.…”