Salicylic Acid Attenuates Virulence in Endovascular Infections by Targeting Global Regulatory Pathways in Staphylococcus Aureus

Authors

Leon Iri Kupferwasser, University of California, Los Angeles
Michael R. Yeaman, University of California, Los Angeles
Cynthia C. Nast, UCLA School of Medicine
Deborah Kupferwasser, University of California, Los Angeles
Yan-Qiong Xiong, University of California, Los Angeles
Marco Palma, Dartmouth College
Ambrose L. Cheung, Dartmouth CollegeFollow
Arnold S. Bayer, University of California, Los AngelesFollow

Document Type

Article

Publication Date

7-15-2003

Publication Title

Journal of Clinical Investigation

Department

Geisel School of Medicine

Abstract

Aspirin has been previously shown to reduce the in vivo virulence of Staphylococcus aureus in experimental endocarditis, through antiplatelet and antimicrobial mechanisms. In the present study, salicylic acid, the major in vivo metabolite of aspirin, mitigated two important virulence phenotypes in both clinical and laboratory S. aureus strains: α-hemolysin secretion and fibronectin binding in vitro. In addition, salicylic acid reduced the expression of the α-hemolysin gene promoter, hla, and the fibronectin gene promoter, fnbA. Transcriptional analysis, fluorometry, and flow cytometry revealed evidence of salicylic acid–mediated activation of the stress-response gene sigB. Expression of the sigB-repressible global regulon sarA and the global regulon agr were also mitigated by salicylic acid, corresponding to the reduced expression of the hla and fnbA genes in vitro. Studies in experimental endocarditis confirmed the key roles of both sarA and sigB in mediating the antistaphylococcal effects of salicylic acid in vivo. Therefore, aspirin has the potential to be an adjuvant therapeutic agent against endovascular infections that result from S. aureus, by downmodulating key staphylococcal global regulons and structural genes in vivo, thus abrogating relevant virulence phenotypes.

DOI

10.1172/JCI16876

Original Citation

Kupferwasser LI, Yeaman MR, Nast CC, et al. Salicylic acid attenuates virulence in endovascular infections by targeting global regulatory pathways in Staphylococcus aureus. J Clin Invest. 2003;112(2):222-233. doi:10.1172/JCI16876

Dartmouth Digital Commons Citation

Kupferwasser, Leon Iri; Yeaman, Michael R.; Nast, Cynthia C.; Kupferwasser, Deborah; Xiong, Yan-Qiong; Palma, Marco; Cheung, Ambrose L.; and Bayer, Arnold S., "Salicylic Acid Attenuates Virulence in Endovascular Infections by Targeting Global Regulatory Pathways in Staphylococcus Aureus" (2003). Dartmouth Scholarship. 3564.
https://digitalcommons.dartmouth.edu/facoa/3564