Control of Streptococcus agalactiae virulence gene.. (CELLCOM-GBS)
Control of Streptococcus agalactiae virulence genes via peptide-based cell to cell communication
Start date: Mar 1, 2013,
End date: Feb 28, 2015
"Quorum sensing (QS) is a bacterial cell-to-cell communication process to control gene expression at population level. Recently, a new QS mechanism was described in streptococci. It involves a transcriptional regulator of the Rgg family and a small hydrophobic peptide (SHP), acting as a signaling molecule. The interaction between SHP and Rgg allows Rgg to control the expression of its target genes. One rgg/shp locus is present in Streptococcus agalactiae (Group B Streptococci), a commensal bacterium in humans, but also a leading cause of devastating infections in newborns and immunocompromised adults. Previously, another team described that Rgg is involved in the regulation of several virulence factors in GBS strain 6313; however, these studies were performed in nutritional rich conditions that are non-optimal for SHP-dependant Rgg activity, and its role in virulence was not addressed. Consequently, we hypothesize that Rgg relevance in GBS pathogeny has been underestimated.Our preliminary results showed that Rgg/SHP system is active in GBS strain NEM316, a newborn isolate. In addition, we found a growth condition that allows high-expression of Rgg/SHP system. The secretome of strain NEM316 and an isogenic rgg-deleted mutant was compared by a label-free proteomic approach. We identified one new target, a secreted protein with a putative transglutaminase (TG) function. This is encoded by all GBS strains sequenced up to now. Virulence experiments showed the implication of the Rgg/SHP system in the full virulence of GBS.The aim of this project will be to better understand this cell-to-cell communication mechanism and clarify its role in GBS pathogenesis. We will also study the function of the already identified target, in vitro and in vivo. Lastly, we will identify new Rgg/SHP targets. We hope that the results obtained will increase the understanding of pathogeny of GBS, opening possible novel approaches to decrease its virulence."
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