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Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds
Authors:Wang Dai  Zetterström Caroline E  Gabrielsen Mads  Beckham Katherine S H  Tree Jai J  Macdonald Sarah E  Byron Olwyn  Mitchell Tim J  Gally David L  Herzyk Pawel  Mahajan Arvind  Uvell Hanna  Burchmore Richard  Smith Brian O  Elofsson Mikael  Roe Andrew J
Institution:Institute of Infection, Immunity, and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Abstract:A class of anti-virulence compounds, the salicylidene acylhydrazides, has been widely reported to block the function of the type three secretion system of several Gram-negative pathogens by a previously unknown mechanism. In this work we provide the first identification of bacterial proteins that are targeted by this group of compounds. We provide evidence that their mode of action is likely to result from a synergistic effect arising from a perturbation of the function of several conserved proteins. We also examine the contribution of selected target proteins to the pathogenicity of Yersinia pseudotuberculosis and to expression of virulence genes in Escherichia coli O157.
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