title: Defining the strain-dependent impact of the Staphylococcal accessory regulator (sarA) on the alpha-toxin phenotype of Staphylococcus aureus.
abstract: We demonstrate that mutation of the staphylococcal accessory regulator (sarA) limits the accumulation of alpha-toxin and phenol-soluble modulins (PSMs) in Staphylococcus aureus isolates of the USA300 clonal lineage. Degradation assays and experiments done with protease inhibitors suggested that this was due to the increased production of extracellular proteases rather than differences associated with the impact of sarA on transcription of the target gene (hla) or the accessory gene regulator (agr). This was confirmed by demonstrating that concomitant mutation of the gene encoding aureolysin (aur) reversed the alpha-toxin and PSM-deficient phenotypes of a USA300 sarA mutant. Mutation of sarA had little impact on the alpha-toxin or PSM phenotypes of the commonly studied strain Newman, which is known to have a mutation in saeS that results in constitutive activation of the saeRS regulatory system, and we also demonstrate that repair of this defect resulted in the increased production of extracellular proteases and reversed both the alpha-toxin and PSM-positive phenotypes of a Newman sarA mutant.
authors.affiliation: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. smeltzermarks@uams.edu
authors.forename: Agnieszka K
authors.initials: AK
authors.lastname: Zielinska
authors.forename: Karen E
authors.initials: KE
authors.lastname: Beenken
authors.forename: Hwang-Soo
authors.initials: HS
authors.lastname: Joo
authors.forename: Lara N
authors.initials: LN
authors.lastname: Mrak
authors.forename: Linda M
authors.initials: LM
authors.lastname: Griffin
authors.forename: Thanh T
authors.initials: TT
authors.lastname: Luong
authors.forename: Chia Y
authors.initials: CY
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Shaw
authors.forename: Mark S
authors.initials: MS
authors.lastname: Smeltzer
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D014644:Genetic Variation; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010636:Phenols / Q000737:chemistry; D010641:Phenotype; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D010636:Phenols; D012329:RNA, Bacterial; D012333:RNA, Messenger; C492107:SarA protein, Staphylococcus aureus; C021091:staphylococcal alpha-toxin