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

Overview

Journal Biochemistry

Specialty Biochemistry

Date 2018 Feb 17

PMID 29451388

Citations 9

Authors

Barbara Hofbauer

Jan Vomacka

Matthias Stahl

Vadim S Korotkov

Megan C Jennings

William M Wuest

Stephan A Sieber

Affiliations

Soon will be listed here.

Abstract

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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