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Sci Rep. 2017 Feb 10;7:42275. doi: 10.1038/srep42275.

Virulence Inhibitors from Brazilian Peppertree Block Quorum Sensing and Abate Dermonecrosis in Skin Infection Models.

Author information

1
Center for the Study of Human Health, Emory University, 550 Asbury Circle, Candler Library 107E, Atlanta, Georgia, USA.
2
Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
3
Department of Dermatology, Emory University School of Medicine, 615 Michael St., Rm 105L WhiteheadBldg, Atlanta, GA, USA.

Abstract

Widespread antibiotic resistance is on the rise and current therapies are becoming increasingly limited in both scope and efficacy. Methicillin-resistant Staphylococcus aureus (MRSA) represents a major contributor to this trend. Quorum sensing controlled virulence factors include secreted toxins responsible for extensive damage to host tissues and evasion of the immune system response; they are major contributors to morbidity and mortality. Investigation of botanical folk medicines for wounds and infections led us to study Schinus terebinthifolia (Brazilian Peppertree) as a potential source of virulence inhibitors. Here, we report the inhibitory activity of a flavone rich extract "430D-F5" against all S. aureus accessory gene regulator (agr) alleles in the absence of growth inhibition. Evidence for this activity is supported by its agr-quenching activity (IC50 2-32 μg mL-1) in transcriptional reporters, direct protein outputs (α-hemolysin and δ-toxin), and an in vivo skin challenge model. Importantly, 430D-F5 was well tolerated by human keratinocytes in cell culture and mouse skin in vivo; it also demonstrated significant reduction in dermonecrosis following skin challenge with a virulent strain of MRSA. This study provides an explanation for the anti-infective activity of peppertree remedies and yields insight into the potential utility of non-biocide virulence inhibitors in treating skin infections.

Conflict of interest statement

C.L.Q. and J.T.L. are named inventors on a provisional patent application concerning the technology presented in this paper. The authors confirm that any competing interests do not alter their adherence to all the Nature Publishing Group policies on sharing data and materials.

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