| Title: | Characterization of MroQ-Dependent Maturation and Export of the Staphylococcus aureus Accessory Gene Regulatory System Autoinducing Peptide |
| Author(s): | Stock MR; Fang L; Johnson KR; Cosgriff C; Teoh WP; Alonzo F; |
| Address: | "Department of Microbiology and Immunology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA. Department of Microbiology and Immunology, University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA" |
| ISSN/ISBN: | 1098-5522 (Electronic) 0019-9567 (Print) 0019-9567 (Linking) |
| Abstract: | "Gram-positive bacteria produce small autoinducing peptides (AIPs), which act to regulate expression of genes that promote adaptive traits, including virulence. The Gram-positive pathogen Staphylococcus aureus generates a cyclic AIP that controls expression of virulence factors via the accessory gene regulatory (Agr) system. S. aureus strains belong to one of four Agr groups (Agr-I, -II, -III, and -IV); each group harbors allelic variants of AgrD, the precursor of AIP. In a prior screen for S. aureus virulence factors, we identified MroQ, a putative peptidase. A DeltamroQ mutant closely resembled a Deltaagr mutant and had significant defects in AIP production in an Agr-I strain. Here, we show that expression of AgrD-I in a DeltamroQ mutant leads to accumulation of an AIP processing intermediate at the membrane that coincides with a loss of secreted mature AIP, indicating that MroQ promotes maturation of AgrD-I. MroQ is conserved in all Agr sequence variants, suggesting either identical function among all Agr types or activity specific to Agr-I strains. Our data indicate that MroQ is required for AIP maturation and activity in Agr-I, -II, and -IV strains irrespective of background. However, MroQ is not required for Agr-III activity despite an identifiable role in peptide maturation. Isogenic Deltaagr and Deltaagr DeltamroQ strains complemented with Agr-I to -IV validated the critical role of MroQ in the generation of active AIP-I, -II, and -IV but not AIP-III. These findings were reinforced by skin infection studies with mice. Our data substantiate the prevailing model that MroQ is a mediator of cyclic peptide maturation" |
| Keywords: | "Mice Animals *Staphylococcus aureus *Peptides, Cyclic Virulence Factors/metabolism Peptide Hydrolases/metabolism Peptides/metabolism Agr MroQ Staphylococcus aureus peptidase peptide pheromone quorum sensing skin infection virulence;" |
| Notes: | "MedlineStock, Madison R Fang, Liwei Johnson, Kaelie R Cosgriff, Chance Teoh, Wei Ping Alonzo, Francis 3rd eng R01 AI120994/AI/NIAID NIH HHS/ R01 AI153059/AI/NIAID NIH HHS/ R01AI120994/HHS | National Institutes of Health (NIH)/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2022/09/09 Infect Immun. 2022 Oct 20; 90(10):e0026322. doi: 10.1128/iai.00263-22. Epub 2022 Sep 8" |
