Virulence-Related Transcriptional Regulators of Streptococcus pyogenes

Excerpt

Control of virulence gene expression in S. pyogenes is under the charge of 13 two-component regulatory systems and at least 30 transcriptional regulators known thus far. These virulence-related regulators are tasked with integrating environmental host cues with the pathogen’s own metabolic state, as well as feedback signals from the expressed genome, into a coordinated response. This overview of the current understanding of S. pyogenes virulence-related regulators describes their roles in one or multiple of the following categories: Master regulators, such as CovR/S and RofA-like proteins (RALPs), that control the activity of multiple virulence-related regulators; Metabolite-responsive regulators, which sense and respond to changes in availability of sources of energy; carbohydrates (CcpA, Mga), amino acid/nitrogen supplies (Rsh, CodY), and other metabolites S. pyogenes must monitor in the host; Metabolic-control regulators, such as VicR/S, MtsR, CiaH/R, that influence expression of metabolism-related genes to maintain the necessary homeostasis to promote colonization; and Environmental/host immunity-responsive regulators, which control responses to a variety of cues, like oxidative stress (PerR), quorum sensing (Rgg2/3), saliva (SalK/R), and neutrophils (Ihk/Irr). Emphasis is made on the interdependence among regulators and the ways in which variation in their connectivity depends on their genotypic background, likely due to coevolution with its human host.