Project description:Trichomonas vaginalis is an extracellular flagellated protozoan responsible for trichomoniasis, one of the most prevalent non-viral sexually transmitted infections. To persist in the host, T. vaginalis employs sophisticated gene regulation mechanisms to adapt to hostile environmental conditions. Although transcriptional regulation is crucial for this adaptation, the specific molecular mechanisms remain poorly understood. Epigenetic regulation, particularly through histone modifications, has emerged as a key modulator of gene expression. Our previous study demonstrated the role of histone modifications H3K4me3 and H3K27Ac in promoting active transcription. However, the full extent of epigenetic regulation in T. vaginalis remained unclear. In this study, we extend these findings by exploring the repressive role of two additional histone H3 modifications, H3K9me3 and H3K27me3. Genome-wide analysis reveals that these modifications are negatively correlated with gene expression, impacting not only protein-coding genes but also repeat genes and transposable elements. These findings offer new insights into the dual role of histone modifications in both activating and repressing gene expression, providing a more comprehensive understanding of epigenetic regulation in T. vaginalis. This expanded knowledge could inform the development of novel therapeutic strategies targeting the epigenetic machinery of this parasite.
Project description:In this study, we investigated genome-wide transcriptional and epigenetic responses of T. vaginalis to histone deacetylase (HDAC) inhibitors.
Project description:We aimed to delineate mechanisms of T. vaginalis resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive T. vaginalis clinical isolates.
Project description:Trichomonas vaginalis is an extracellular flagellated protozoan responsible for trichomoniasis, one of the most prevalent non-viral sexually transmitted infections. To persist in the host, T. vaginalis employs sophisticated gene regulation mechanisms to adapt to hostile environmental conditions. Although transcriptional regulation is crucial for this adaptation, the specific molecular mechanisms remain poorly understood. Epigenetic regulation, particularly through histone modifications, has emerged as a key modulator of gene expression. Our previous study demonstrated the role of histone modifications H3K4me3 and H3K27Ac in promoting active transcription. However, the full extent of epigenetic regulation in T. vaginalis remained unclear. In this study, we extend these findings by exploring the repressive role of two additional histone H3 modifications, H3K9me3 and H3K27me3. Genome-wide analysis reveals that these modifications are negatively correlated with gene expression, impacting not only protein-coding genes but also repeat genes and transposable elements. These findings offer new insights into the dual role of histone modifications in both activating and repressing gene expression, providing a more comprehensive understanding of epigenetic regulation in T. vaginalis. This expanded knowledge could inform the development of novel therapeutic strategies targeting the epigenetic machinery of this parasite.
Project description:Recurrent urinary tract infections (rUTI) are a costly clinical problem affecting millions of women worldwide each year. The majority of rUTI cases are caused by uropathogenic Escherichia coli (UPEC). Data from humans and mouse models indicate that some instances of rUTI are caused by UPEC emerging from latent reservoirs in the bladder. Some studies have reported that women with vaginal dysbiosis, typically characterized by high levels of Gardnerella vaginalis and other anaerobes, are at increased risk of UTI. Multiple studies have detected G. vaginalis in urine collected by transurethral catheterization (to limit vaginal contamination), suggesting that some women experience routine urinary tract exposures. We recently reported that inoculation of G. vaginalis into the bladder triggers rUTI from UPEC bladder reservoirs in a mouse model. Here we performed whole bladder RNAseq to identify host pathways involved in G. vaginalis-induced rUTI. We identified multiple host pathways differentially expressed following G. vaginalis exposure. At the gene and transcript level, we identified upregulation of the orphan nuclear receptor Nur77 (aka Nr4a1) and Nur77-regulated genes. Pilot data from Nur77 knockout mice suggests that Nur77 is necessary for G. vaganalis exposure to trigger rUTI.
Project description:To elucidate the molecular pathways altered by host-microbe interactions in cervicovaginal epithelial cells we performed whole genome RNA-sequencing. We identified genes and functional pathways that were altered in cervicovaginal epithelial cells after exposure to G. vaginalis or L. crispatus or their supernatant.
