SarA plays a predominant role in controlling the production of extracellular proteases in the diverse clinical isolates of Staphylococcus aureus LAC and UAMS-1

Virulence

Stephanie D. Byrum¹  Alan J. Tackett¹  Brittney D. Gimza²  Lindsey N. Shaw²  Aura M. Ramirez³  Mark S. Smeltzer³  Karen E. Beenken³ 

[1] Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, and Arkansas Children’s Research Institute, Little Rock, AR, US;Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, F;Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR, US;

关键词: Staphylococcus aureus;    extracellular protease;    regulation;    biofilm;    sarA;    rot;    mgrA;    sarS;    sarZ;    sarR;   

DOI  :  10.1080/21505594.2020.1855923

来源: Taylor & Francis

【 摘 要 】

Using DNA affinity chromatography we demonstrate that the S. aureus regulatory proteins MgrA, Rot, SarA, and SarS bind DNA baits derived from the promoter regions associated with the genes encoding aureolysin, ScpAB, SspABC, and SplA-F. Three of four baits also bound SarR and SarZ, the exception in both cases being the ScpAB-associated bait. Using the USA300, methicillin-resistant strain LAC and the USA200, methicillin-sensitive strain UAMS-1, we generated mutations in the genes encoding each of these proteins alone and in combination with sarA and examined the impact on protease production, the accumulation of high molecular weight proteins, and biofilm formation. These studies confirmed that multiple regulatory loci are involved in limiting protease production to a degree that impacts all of these phenotypes, but also demonstrate that sarA plays a predominant role in this regard. Using sarA mutants unable to produce individual proteases alone and in combination with each other, we also demonstrate that the increased production of aureolysin and ScpA is particularly important in defining the biofilm-deficient phenotype of LAC and UAMS-1 sarA mutants, while aureolysin alone plays a key role in defining the reduced accumulation of alpha toxin and overall cytotoxicity as assessed using both osteoblasts and osteoclasts.

【 授权许可】

CC BY