ω-Hydroxyemodin Limits Staphylococcus aureus Quorum Sensing-Mediated Pathogenesis and Inflammation

• DOI: 10.1128/aac.04564-14
• Publication Date: 2015-02-03T06:04:54Z
• Authors: Seth M. Daly; Bradley O. Elmore; Jeffrey S. Kavanaugh; Kathleen D. Triplett; Mario Figueroa; Huzefa A. Raja; Tamam El-Elimat; Heidi A. Crosby; Jon K. Femling; Nadja B. Cech; Alexander R. Hors...; Nicholas H. Oberlies; Pamela R. Hall
• Keywords: Pathogenesis; Virulence factor

Antibiotic-resistant pathogens are a global health threat. Small molecules that inhibit bacterial virulence have been suggested as alternatives or adjuncts to conventional antibiotics, they may limit pathogenesis and increase susceptibility host killing. Staphylococcus aureus is major cause of invasive skin soft tissue infections (SSTIs) in both the hospital community settings, it also becoming increasingly antibiotic resistant. Quorum sensing (QS) mediated by accessory gene regulator (agr) controls factor production essential for causing SSTIs. We recently identified ω-hydroxyemodin (OHM), polyhydroxyanthraquinone isolated from solid-phase cultures Penicillium restrictum, suppressor QS compound sought further characterization mechanism action. At concentrations nontoxic eukaryotic cells subinhibitory growth, OHM prevented agr signaling all four S. alleles. inhibited direct binding AgrA, response encoded operon, preventing interaction AgrA with P2 promoter. Importantly, was efficacious mouse model SSTI. Decreased dermonecrosis treatment associated enhanced clearance reductions inflammatory cytokine transcription expression at site infection. Furthermore, immune cell killing vitro an agr-dependent manner. These data suggest disarmament through suppression bolster innate inflammation.