Regulation of toxic shock syndrome toxin‐1 by the accessory gene regulator in Staphylococcus aureus is mediated by the repressor of toxins

• Published in: Molecular microbiology Vol. 112; no. 4; pp. 1163 - 1177
• Main Authors: Tuffs, Stephen W., Herfst, Christine A., Baroja, Miren L., Podskalniy, Vladyslav A., DeJong, Erica N., Coleman, Charlotte E. M., McCormick, John K.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2019
• Subjects: Complementation; Exotoxins; Gene deletion; Gene expression; Menopause; Menstruation; Product safety; Rot; Sag; Septic shock; Staphylococcal enterotoxin F; Staphylococcus aureus; Toxic shock syndrome; Toxins; Transcription
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.14353

Summary Toxic shock syndrome toxin‐1 (TSST‐1) is a superantigen (SAg) produced by Staphylococcus aureus thought to be responsible for essentially all cases of menstrual‐associated toxic shock syndrome (TSS). As a potent exotoxin, it is not surprising that S. aureus has evolved multiple systems to control expression of TSST‐1. Although the accessory gene regulator (Agr) system is recognized to enhance TSST‐1 expression, how Agr regulates TSST‐1 is unclear. Using an agr‐null mutant, complementation experiments demonstrated that Agr controls TSST‐1 expression through the activity of the RNAIII effector molecule. RNAIII can repress translation of the repressor of toxins (Rot) regulator, and deletion of rot increased expression of TSST‐1 during the exponential phase of growth. Deletion of agr did not affect rot transcription, but did result in overexpression of the Rot protein, and Rot was also shown to bind and positively regulate the rot promoter. Overexpression of Rot dramatically repressed TSST‐1, and Rot bound directly to the TSST‐1 promoter. Deletion of both agr and rot in S. aureus returned TSST‐1 expression to wild‐type levels. This work demonstrates that Agr, although widely considered to be an inducer of TSST‐1, has evolved in combination with Rot, to restrict the expression of this potent SAg. Toxic shock syndrome toxin‐1 (TSST‐1) is a potent Staphylococcus aureus superantigen regulated by the quorum‐sensing accessory gene regulator (Agr) system, yet how Agr regulates TSST‐1 is unclear. This work demonstrates that Agr controls TSST‐1 expression through the repressor of toxins (Rot), and although Agr is widely considered to be an inducer of TSST‐1, Agr functions in combination with Rot to restrict TSST‐1 expression at low cell density.