Project description:Bacteria assume distinct lifestyles during the planktonic and biofilm modes of growth. In biofilms, they are more tolerant to antibiotics and can evade the immune system response more effectively. However, little is known regarding the molecular determinants involved in biofilm formation by Gardnerella vaginali, the predominant species found in bacterial vaginosis (BV). Hence, to gain insight into the pathogenesis of G. vaginalis, we carried out a comparative transcriptomic analysis between planktonic and biofilm phenotypes, using RNA-sequencing. The major alterations observed were related with the transcription of genes involved in cell wall biogenesis and typical stress factors, in which was found significantly up-regulated in biofilms, resulting in a protected mode of bacterial growth. In addition, biofilm phenotype was characterized by low metabolic activity, which is appropriate to guarantee long term survival during BV recurrence.
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.
