Dual Inhibitor of Staphylococcus aureus Virulence and Biofilm Attenuates Expression of Major Toxins and Adhesins.

Biochemistry

Department of Chemistry, Chair of Organic Chemistry II, Center for Integrated Protein Science (CIPSM), Institute of Advanced Studies (IAS) , Technische Universität München (TUM), Lichtenbergstraße 4 , D-85747 Garching , Germany.

Published: March 2018

Staphylococcus aureus is a major bacterial pathogen that invades and damages host tissue by the expression of devastating toxins. We here performed a phenotypic screen of 35 molecules that were structurally inspired by previous hydroxyamide-based S. aureus virulence inhibitors compiled from commercial sources or designed and synthesized de novo. One of the most potent compounds, AV73, not only reduced hemolytic alpha-hemolysin production in S. aureus but also impeded in vitro biofilm formation. The effect of AV73 on bacterial proteomes and extracellular protein levels was analyzed by quantitative proteomics and revealed a significant down-regulation of major virulence and biofilm promoting proteins. To elucidate the mode of action of AV73, target identification was performed using affinity-based protein profiling (AfBPP), where among others YidC was identified as a target.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462815PMC
http://dx.doi.org/10.1021/acs.biochem.7b01271DOI Listing

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