title: Staphylococcus epidermidis agr quorum-sensing system: signal identification, cross talk, and importance in colonization.
abstract: Staphylococcus epidermidis is an opportunistic pathogen that is one of the leading causes of medical device infections. Global regulators like the agr quorum-sensing system in this pathogen have received a limited amount of attention, leaving important questions unanswered. There are three agr types in S. epidermidis strains, but only one of the autoinducing peptide (AIP) signals has been identified (AIP-I), and cross talk between agr systems has not been tested. We structurally characterized all three AIP types using mass spectrometry and discovered that the AIP-II and AIP-III signals are 12 residues in length, making them the largest staphylococcal AIPs identified to date. S. epidermidis agr reporter strains were developed for each system, and we determined that cross-inhibitory interactions occur between the agr type I and II systems and between the agr type I and III systems. In contrast, no cross talk was observed between the type II and III systems. To further understand the outputs of the S. epidermidis agr system, an RNAIII mutant was constructed, and microarray studies revealed that exoenzymes (Ecp protease and Geh lipase) and low-molecular-weight toxins were downregulated in the mutant. Follow-up analysis of Ecp confirmed the RNAIII is required to induce protease activity and that agr cross talk modulates Ecp activity in a manner that mirrors the agr reporter results. Finally, we demonstrated that the agr system enhances skin colonization by S. epidermidis using a porcine model. This work expands our knowledge of S. epidermidis agr system function and will aid future studies on cell-cell communication in this important opportunistic pathogen.
authors: Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors: Michael E
authors: ME
authors: Olson
authors: Department of Chemistry and Biochemistry, University of North Carolina Greensboro, Greensboro, North Carolina, USA.
authors: Daniel A
authors: DA
authors: Todd
authors: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors: Carolyn R
authors: CR
authors: Schaeffer
authors: Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors: Alexandra E
authors: AE
authors: Paharik
authors: Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
authors: Michael J
authors: MJ
authors: Van Dyke
authors: Institute for Medical Microbiology, Virology and Hygiene, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors: Henning
authors: H
authors: Büttner
authors: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA.
authors: Paul M
authors: PM
authors: Dunman
authors: Institute for Medical Microbiology, Virology and Hygiene, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors: Holger
authors: H
authors: Rohde
authors: Department of Chemistry and Biochemistry, University of North Carolina Greensboro, Greensboro, North Carolina, USA.
authors: Nadja B
authors: NB
authors: Cech
authors: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
authors: Paul D
authors: PD
authors: Fey
authors: Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA alex-horswill@uiowa.edu.
authors: Alexander R
authors: AR
authors: Horswill
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D010456:Peptides, Cyclic / Q000235:genetics / Q000378:metabolism*; D053038:Quorum Sensing; D013203:Staphylococcal Infections / Q000382:microbiology*; D013212:Staphylococcus epidermidis / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D013552:Swine
chemical_list: C414532:AgrD protein, Staphylococcus; D001426:Bacterial Proteins; D010456:Peptides, Cyclic