Project description:We applied Formaldehyde-Assisted Isolation of Regulatory Elements enrichment followed by sequencing (FAIRE-Seq) to generate genome-wide temporal chromatin maps of Chlamydia trachomatis-infected human epithelial cells in vitro over the chlamydial developmental cycle. We detected both conserved and distinct temporal regions of chromatin accessibility associated with C. trachomatis infection. The observed differentially accessible chromatin regions, including several Clusters of Open Regulatory Elements (COREs) and temporally-enriched sets of transcription factors, may help shape the host cell response to infection. These regions and motifs were linked to genomic features and genes associated with immune responses, re-direction of host cell nutrients, intracellular signaling, cell-cell adhesion, extracellular matrix, metabolism and apoptosis. This work will serve as a basis for future functional studies of transcriptional regulation and epigenomic regulatory elements in Chlamydia-infected human cells.
Project description:<p>Chlamydia trachomatis, an intracellular pathogen, is recognized as the most common sexually transmitted bacterial infection among women worldwide. Chlamydia infections can lead to undesirable clinical outcomes, including pelvic inflammatory disease and infertility. Recently, the gut has been identified as a niche for Chlamydia colonization; however, despite the biological impact on the host remaining under investigation, oral inoculation of Chlamydia as a whole-organism vaccine has been reported as a promising strategy for preventing genital Chlamydia infections. Few studies have evaluated the impact of oral Chlamydia vaccination on the gut microbiome and metabolite changes. In this study, we assessed time-series alterations in the gut microbiome and metabolites following oral Chlamydia inoculation, and we analyzed the composition and correlation between serum immune parameters and the sequencing profiles in the host. We identified 129 microbial changes and 186 significantly different metabolites in the gut across various vaccination approaches during the 30-day immunization process. Additionally, we discussed potential biomarkers of effective immunization based on correlation analysis.</p>
Project description:Experimental screening of a compound library identified a molecule that potently inhibits the growth of the obligate intracellular bacterial pathogen Chlamydia trachomatis in human cells. To identify the molecular target of the compound, three mutant bacterial strains resistant to its inhibitory action were generated by long-term passage in the presence of initially low but increasing concentrations of the molecule. Subsequently, genomic DNA of the three mutant and the wildtype bacteria was isolated and subjected to whole genome sequencing to identify resistance-promoting mutations.
