Impact of the functional status of saeRS on in vivo phenotypes of Staphylococcus aureus sarA mutants. Issue 6 (12th May 2014)

• Record Type: Journal Article
• Authors: Beenken, Karen E.; Mrak, Lara N.; Zielinska, Agnieszka K.; Atwood, Danielle N.; Loughran, Allister J.; Griffin, Linda M.; Matthews, K. Alice; Anthony, Allison M.; Spencer, Horace J.; Skinner, Robert A.; Post, Ginell R.; Lee, Chia Y.; Smeltzer, Mark S.
• Is Part Of: Molecular microbiology. Volume 92:Issue 6(2014)
• Page Start: 1299
• Page End: 1312
• Publication Date: 2014-05-12
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12629
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>We investigated the <italic>in vivo</italic> relevance of the impact of <italic>sarA</italic> and <italic>saeRS</italic> on protease production using derivatives of the USA300 strain LAC. The results confirmed that mutation of <italic>saeRS</italic> or <italic>sarA</italic> reduces virulence in a bacteremia model to a comparable degree. However, while eliminating protease production restored virulence in the <italic>sarA</italic> mutant, it had little impact in the <italic>saeRS</italic> mutant. Additionally, constitutive activation of <italic>saeRS</italic> (<italic>saeRS<sup>C</sup></italic>) enhanced the virulence of LAC and largely restored virulence in the isogenic <italic>sarA</italic> mutant. Based on these results, together with our analysis of the representative virulence factors alpha toxin, protein A (Spa), and extracellular nucleases, we propose a model in which the attenuation of <italic>saeRS</italic> mutants is defined primarily by decreased production of such factors, while constitutive activation of <italic>saeRS</italic> increases virulence, and reverses the attenuation of <italic>sarA</italic> mutants, because it results in both increased production and decreased protease‐mediated degradation of these same factors. This regulatory balance was also apparent in a murine model of catheter‐associated infection, with the results suggesting that the impact of <italic>saeRS</italic> on nuclease production plays an important role during the early stages of these infections that is partially offset by increased protease production in <italic>sarA</italic> mutants.</p> </abstract>