Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds

Dai Wang; Caroline E Zetterström; Mads Gabrielsen; Katherine S H Beckham; Jai J Tree; Sarah E Macdonald; Olwyn Byron; Tim J Mitchell; David L Gally; Pawel Herzyk; Arvind Mahajan; Hanna Uvell; Richard Burchmore; Brian O Smith; Mikael Elofsson; Andrew J Roe

doi:10.1074/jbc.M111.233858

Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds

Dai Wang, Caroline E Zetterström, Mads Gabrielsen, Katherine S H Beckham, Jai J Tree, Sarah E Macdonald, Olwyn Byron, Tim J Mitchell, David L Gally, Pawel Herzyk, Arvind Mahajan, Hanna Uvell, Richard Burchmore, Brian O Smith, Mikael Elofsson, Andrew J Roe

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

78 Citations (Scopus)

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.

Original language	English
Pages (from-to)	29922-31
Number of pages	10
Journal	Journal of Biological Chemistry
Volume	286
Issue number	34
DOIs	https://doi.org/10.1074/jbc.M111.233858
Publication status	Published - 26 Aug 2011

Keywords

Anti-Bacterial Agents
Escherichia coli Infections
Escherichia coli O157
Gene Expression Regulation, Bacterial
Hydrazines
Virulence Factors
Yersinia pseudotuberculosis
Yersinia pseudotuberculosis Infections

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10.1074/jbc.M111.233858

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Wang, D., Zetterström, C. E., Gabrielsen, M., Beckham, K. S. H., Tree, J. J., Macdonald, S. E., Byron, O., Mitchell, T. J., Gally, D. L., Herzyk, P., Mahajan, A., Uvell, H., Burchmore, R., Smith, B. O., Elofsson, M., & Roe, A. J. (2011). Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds. Journal of Biological Chemistry, 286(34), 29922-31. https://doi.org/10.1074/jbc.M111.233858

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title = "Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds",

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.",

keywords = "Anti-Bacterial Agents, Escherichia coli Infections, Escherichia coli O157, Gene Expression Regulation, Bacterial, Hydrazines, Virulence Factors, Yersinia pseudotuberculosis, Yersinia pseudotuberculosis Infections",

author = "Dai Wang and Zetterstr{\"o}m, {Caroline E} and Mads Gabrielsen and Beckham, {Katherine S H} and Tree, {Jai J} and Macdonald, {Sarah E} and Olwyn Byron and Mitchell, {Tim J} and Gally, {David L} and Pawel Herzyk and Arvind Mahajan and Hanna Uvell and Richard Burchmore and Smith, {Brian O} and Mikael Elofsson and Roe, {Andrew J}",

year = "2011",

month = aug,

day = "26",

doi = "10.1074/jbc.M111.233858",

language = "English",

volume = "286",

pages = "29922--31",

journal = "Journal of Biological Chemistry",

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publisher = "American Society for Biochemistry and Molecular Biology",

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Wang, D, Zetterström, CE, Gabrielsen, M, Beckham, KSH, Tree, JJ, Macdonald, SE, Byron, O, Mitchell, TJ, Gally, DL, Herzyk, P, Mahajan, A, Uvell, H, Burchmore, R, Smith, BO, Elofsson, M & Roe, AJ 2011, 'Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds', Journal of Biological Chemistry, vol. 286, no. 34, pp. 29922-31. https://doi.org/10.1074/jbc.M111.233858

TY - JOUR

T1 - Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds

AU - Wang, Dai

AU - Zetterström, Caroline E

AU - Gabrielsen, Mads

AU - Beckham, Katherine S H

AU - Tree, Jai J

AU - Macdonald, Sarah E

AU - Byron, Olwyn

AU - Mitchell, Tim J

AU - Gally, David L

AU - Herzyk, Pawel

AU - Mahajan, Arvind

AU - Uvell, Hanna

AU - Burchmore, Richard

AU - Smith, Brian O

AU - Elofsson, Mikael

AU - Roe, Andrew J

PY - 2011/8/26

Y1 - 2011/8/26

N2 - 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.

AB - 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.

KW - Anti-Bacterial Agents

KW - Escherichia coli Infections

KW - Escherichia coli O157

KW - Gene Expression Regulation, Bacterial

KW - Hydrazines

KW - Virulence Factors

KW - Yersinia pseudotuberculosis

KW - Yersinia pseudotuberculosis Infections

U2 - 10.1074/jbc.M111.233858

DO - 10.1074/jbc.M111.233858

M3 - Article

C2 - 21724850

SN - 0021-9258

VL - 286

SP - 29922

EP - 29931

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 34

ER -

Identification of bacterial target proteins for the salicylidene acylhydrazide class of virulence-blocking compounds

Abstract

Keywords

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