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.
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| http://dx.doi.org/10.1128/JB.01517-10 | DOI Listing |
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Article Synopsis
- - The study shows that mutating the staphylococcal accessory regulator A (sarA) in the USA300 strain LAC significantly reduces virulence in a mouse model for osteomyelitis more effectively than altering the accessory gene regulator (agr), regardless of the status of another gene (likely referring to a specific gene related to virulence).
- - The researchers found that protease production decreased in the sarA mutant, whereas it increased in the agr and another mutant; these changes affected biofilm formation and cytotoxicity of conditioned medium (CM) against bone cells.
- - The research concluded that increased production of extracellular proteases limits the effectiveness of key virulence factors, such as toxins, thereby reducing the overall virulence
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