Chlamydia trachomatis (C. trachomatis) is the most common etiological agent of bacterial sexually transmitted infections (STIs) worldwide and causes serious health sequelae such as cervicitis, pelvic inflammatory disease, and even infertility if ascending from the lower to the upper female genital tract. Previous studies have revealed the pivotal role of vaginal microbiota in susceptibility to STIs. However, alterations in the vaginal microbiota in women who are infertile and infected with C. trachomatis remain unknown. This study used metagenomic analysis of sequenced 16S rRNA gene amplicons to examine the vaginal microbial profiles of women with tubal infertility who were C. trachomatis-negative and those who were C. trachomatis-positive pre- and post-antibiotic treatment. Women who were C. trachomatis-negative and deemed healthy were recruited as references of eubiosis and dysbiosis. Women with tubal infertility and C. trachomatis infection presented a unique Lactobacillus iners-dominated vaginal microbiota rather than one dominated by Lactobacillus crispatus and displayed a decrease in Lactobacillus, Bifidobacterium, Enterobacter, Atopobium, and Streptococcus, accompanied by decreased levels of cytokines such as interferon (IFN)-γ and interleukin (IL)-10. This altered vaginal microbiota could be restored with varying degrees after standard treatment for C. trachomatis. This shift could be a predictive vaginal microbiota signature for C. trachomatis infection among females with tubal infertility, while no significant differences in phylum, class, and operational taxonomic unit (OTU) levels were observed between women with tubal infertility who were C. trachomatis-negative and healthy controls. This is the first study to provide data on the association of vaginal microbiota with C. trachomatis infection among women with tubal infertility and highlights unprecedented potential opportunities to predict C. trachomatis infection.

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Chlamydia trachomatis has evolved strategies to prevent host cell apoptosis to evade the host immune defense. However, the precise mechanisms of antiapoptotic activity of C. trachomatis still need to be clarified. Pgp3, one of eight plasmid proteins of C. trachomatis, has been identified to be closely associated with chlamydial virulence. In this study, we attempted to explore the effects and the mechanisms of Pgp3 protein on apoptosis in HeLa cells; the results showed that Pgp3 increased Bcl-2/Bax ratio and prevented caspase-3 activation to suppress apoptosis induced by TNF-α and cycloheximide (CHX) through ERK1/2 pathway activation. Downregulation of DJ-1 with siRNA-DJ-1(si-DJ-1) reduced ERK1/2 phosphorylation and elevated apoptotic rate significantly in Pgp3-HeLa cells. However, inhibition of ERK1/2 signal pathway with ERK inhibitor PD98059 had little effect on DJ-1 expression. These findings confirm that plasmid protein Pgp3 contributes to apoptosis resistance through ERK1/2 signal pathway mediated by upregulation of DJ-1 expression. Therefore, the present study provided novel insights into the role of Pgp3 in apoptosis and suggested that manipulation of the host apoptosis response could be a new approach for the prevention and treatment of C. trachomatis infection.

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Long non-coding RNAs (lncRNAs) have been demonstrated to play essential roles in many diseases. However, few studies have shown that lncRNAs take part in the pathogenesis of Chlamydia trachomatis (C. trachomatis). Here, we used a lncRNA microarray to detect the global lncRNA expression profiles in HeLa cells transfected with pORF5 plasmid protein, an important virulence factor for C. trachomatis. The differentially expressed lncRNAs and mRNAs screened by microarray were selected for validation by quantitative real-time PCR. The up-regulated lncRNA zinc finger antisense 1 (ZFAS1) was presumed to involved in MAPK pathways by bioinformatics analysis. Inhibition of ZFAS1 decreased the apoptotic rate of pORF5 and reduced the infectivity of C. trachomatis, and MAPK/p38 pathway was involved in anti-apoptotic effect induced by ZFAS1. Therefore, the present study confirmed that pORF5 up-regulates ZFAS1 to promote host cell survival via MAPK/p38 pathway and influences the infectivity of C. trachomatis.