| Title: | "PepO, a CovRS-controlled endopeptidase, disrupts Streptococcus pyogenes quorum sensing" |
| Author(s): | Wilkening RV; Chang JC; Federle MJ; |
| Address: | "Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60607, USA. Department of Medicinal Chemistry and Pharmacognosy, Center for Biomolecular Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, 60607, USA" |
| ISSN/ISBN: | 1365-2958 (Electronic) 0950-382X (Print) 0950-382X (Linking) |
| Abstract: | "Group A Streptococcus (GAS, Streptococcus pyogenes) is a human-restricted pathogen with a capacity to both colonize asymptomatically and cause illnesses ranging from pharyngitis to necrotizing fasciitis. An understanding of how and when GAS switches between genetic programs governing these different lifestyles has remained an enduring mystery and likely requires carefully tuned environmental sensors to activate and silence genetic schemes when appropriate. Herein, we describe the relationship between the Control of Virulence (CovRS, CsrRS) two-component system and the Rgg2/3 quorum-sensing pathway. We demonstrate that responses of CovRS to the stress signals Mg(2+) and a fragment of the antimicrobial peptide LL-37 result in modulated activity of pheromone signaling of the Rgg2/3 pathway through a means of proteolysis of SHP peptide pheromones. This degradation is mediated by the cytoplasmic endopeptidase PepO, which is the first identified enzymatic silencer of an RRNPP-type quorum-sensing pathway. These results suggest that under conditions in which the virulence potential of GAS is elevated (i.e. enhanced virulence gene expression), cellular responses mediated by the Rgg2/3 pathway are abrogated and allow individuals to escape from group behavior. These results also indicate that Rgg2/3 signaling is instead functional during non-virulent GAS lifestyles" |
| Keywords: | Antimicrobial Cationic Peptides/metabolism Bacterial Proteins/metabolism Endopeptidases/*metabolism Gene Regulatory Networks Histidine Kinase Intracellular Signaling Peptides and Proteins/metabolism Magnesium/metabolism Pheromones/*metabolism *Quorum Sens; |
| Notes: | "MedlineWilkening, Reid V Chang, Jennifer C Federle, Michael J eng R01 AI091779/AI/NIAID NIH HHS/ R01-AI091779/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2015/09/30 Mol Microbiol. 2016 Jan; 99(1):71-87. doi: 10.1111/mmi.13216. Epub 2015 Oct 14" |
