4.6 Article

Identification of Bacterial Target Proteins for the Salicylidene Acylhydrazide Class of Virulence-blocking Compounds

Journal

JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 286, Issue 34, Pages 29922-29931

Publisher

ELSEVIER
DOI: 10.1074/jbc.M111.233858

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Funding

  1. Medical Research Scotland [223 ORG]
  2. Biotechnology and Biological Sciences Research Council (Swindon, United Kingdom) [BB/G011389/1]
  3. Swedish Research Council
  4. Wellcome Trust
  5. Knut and Alice Wallenberg Foundation
  6. Vinnova
  7. BBSRC [BB/G011389/1] Funding Source: UKRI
  8. Biotechnology and Biological Sciences Research Council [BB/G011389/1] Funding Source: researchfish

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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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