title: Staphylococcus aureus nuclease is an SaeRS-dependent virulence factor.
abstract: Several prominent bacterial pathogens secrete nuclease (Nuc) enzymes that have an important role in combating the host immune response. Early studies of Staphylococcus aureus Nuc attributed its regulation to the agr quorum-sensing system. However, recent microarray data have indicated that nuc is under the control of the SaeRS two-component system, which is a major regulator of S. aureus virulence determinants. Here we report that the nuc gene is directly controlled by the SaeRS two-component system through reporter fusion, immunoblotting, Nuc activity measurements, promoter mapping, and binding studies, and additionally, we were unable identify a notable regulatory link to the agr system. The observed SaeRS-dependent regulation was conserved across a wide spectrum of representative S. aureus isolates. Moreover, with community-associated methicillin-resistant S. aureus (CA MRSA) in a mouse model of peritonitis, we observed in vivo expression of Nuc activity in an SaeRS-dependent manner and determined that Nuc is a virulence factor that is important for in vivo survival, confirming the enzyme's role as a contributor to invasive disease. Finally, natural polymorphisms were identified in the SaeRS proteins, one of which was linked to Nuc regulation in a CA MRSA USA300 endocarditis isolate. Altogether, our findings demonstrate that Nuc is an important S. aureus virulence factor and part of the SaeRS regulon.
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: Tyler K
authors: TK
authors: Nygaard
authors: Laynez
authors: L
authors: Ackermann
authors: Robert L
authors: RL
authors: Watkins
authors: Oliwia W
authors: OW
authors: Zurek
authors: Kyler B
authors: KB
authors: Pallister
authors: Shannon
authors: S
authors: Griffith
authors: Megan R
authors: MR
authors: Kiedrowski
authors: Caralyn E
authors: CE
authors: Flack
authors: Jeffrey S
authors: JS
authors: Kavanaugh
authors: Barry N
authors: BN
authors: Kreiswirth
authors: Alexander R
authors: AR
authors: Horswill
authors: Jovanka M
authors: JM
authors: Voyich
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D008836:Micrococcal Nuclease / Q000096:biosynthesis*; D010538:Peritonitis / Q000382:microbiology / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism*; D018085:Regulon; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity*; D014157:Transcription Factors; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; C433805:SaeR protein, Staphylococcus aureus; D014157:Transcription Factors; D037521:Virulence Factors; D011494:Protein Kinases; C527351:SaeS protein, Staphylococcus aureus; D008836:Micrococcal Nuclease
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