title: Staphylococcus aureus regulates the expression and production of the staphylococcal superantigen-like secreted proteins in a Rot-dependent manner.
abstract: Staphylococcus aureus overproduces a subset of immunomodulatory proteins known as the staphylococcal superantigen-like proteins (Ssls) under conditions of pore-mediated membrane stress. In this study we demonstrate that overproduction of Ssls during membrane stress is due to the impaired activation of the two-component module of the quorum-sensing accessory gene regulator (Agr) system. Agr-dependent repression of ssl expression is indirect and mediated by the transcription factor repressor of toxins (Rot). Surprisingly, we observed that Rot directly interacts with and activates the ssl promoters. The role of Agr and Rot as regulators of ssl expression was observed across several clinically relevant strains, suggesting that overproduction of immunomodulatory proteins benefits agr-defective strains. In support of this notion, we demonstrate that Ssls contribute to the residual virulence of S. aureus lacking agr in a murine model of systemic infection. Altogether, these results suggest that S. aureus compensates for the inactivation of Agr by producing immunomodulatory exoproteins that could protect the bacterium from host-mediated clearance.
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Benson
authors.forename: Sarit
authors.initials: S
authors.lastname: Lilo
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wasserman
authors.forename: Matthew
authors.initials: M
authors.lastname: Thoendel
authors.forename: Amanda
authors.initials: A
authors.lastname: Smith
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Horswill
authors.forename: John
authors.initials: J
authors.lastname: Fraser
authors.forename: Richard P
authors.initials: RP
authors.lastname: Novick
authors.forename: Bo
authors.initials: B
authors.lastname: Shopsin
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Torres
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D004269:DNA, Bacterial / Q000235:genetics; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D012376:Rodent Diseases / Q000382:microbiology / Q000473:pathology; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D018089:Superantigens / Q000096:biosynthesis*; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012097:Repressor Proteins; D018089:Superantigens; D037521:Virulence Factors; C408643:rot protein, Staphylococcus aureus