Project description:An anaerobe-dominant, Lactobacillus-deplete cervicovaginal microbiome is associated with adverse reproductive outcomes. Gardnerella vaginalis, a common cervicovaginal anaerobe, alters cervicovaginal epithelial cell function, resulting in inflammatory immune responses and epithelial barrier breakdown. Specific host-microbial mechanisms inducing this epithelial dysfunction remain unknown. Here we show microbe-specific alterations in cervicovaginal epithelial cell metabolite profiles where G. vaginalis, but not Lactobacillus crispatus, increases polyamine biosynthesis. Pretreatment with polyamines (putrescine, spermidine and spermine) globally shifts G. vaginalis-induced transcriptomic profiles. Alterations in transcripts encoding enzymes responsible for polyamine synthesis and catabolism provides further evidence that G. vaginalis modifies polyamine biosynthesis. Additionally, polyamine-mediated transcriptomic changes include genes related to bacterial defense, inflammation, and epigenetic processes. Polyamines mitigate G. vaginalis-induced inflammatory responses through reduction of cytokines, chemokines, and matrix metalloproteinases. The ability of cervicovaginal metabolites to alter microbe-mediated changes in epithelial cell function suggests that metabolite-microbe interactions are critical mediators of epithelial defense against a Lactobacillus-deplete microbiota.
Project description:Transcriptional profiling of mouse gut wall tissue following infection with Salmonella or treatment with Probiotics to see the role of probiotics in preventing salmonella infection through gut mucosal route of mouse.
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.
