Characterisation of the effects of salicylidene acylhydrazide compounds on type three secretion in Escherichia coli O157:H7

Tree, J.J., Wang, D., McInally, C., Mahajan, A., Layton, A., Houghton, I., Elofsson, M., Stevens, M.P., Gally, D.L. and Roe, A.J. (2009) Characterisation of the effects of salicylidene acylhydrazide compounds on type three secretion in Escherichia coli O157:H7. Infection and Immunity, 77(10), pp. 4209-4220. (doi: 10.1128/IAI.00562-09) (PMID:19635828) (PMCID:PMC2747932)

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Abstract

Recent work has highlighted a number of compounds that target bacterial virulence by affecting gene regulation. In this work, we show that small-molecule inhibitors affect the expression of the type III secretion system (T3SS) of <i>Escherichia coli</i> O157:H7 in liquid culture and when the bacteria are attached to bovine epithelial cells. The inhibition of T3SS expression resulted in a reduction in the capacity of the bacteria to form attaching and effacing lesions. Our results show a marked variation in the ability of four structurally-related compounds to inhibit the T3SS of a panel of isolates. Using transcriptomics, we provide a comprehensive analysis of the conserved- and inhibitor-specific transcriptional responses to the four compounds. These analyses of gene expression show that numerous virulence genes, located on horizontally-acquired DNA elements, are affected by the compounds but the number of genes significantly affected varied markedly between the compounds. Overall, we highlight the importance of assessing the effect of such "anti-virulence" agents on a range of isolates and discuss the possible mechanisms which may lead to the co-ordinate down-regulation of horizontally acquired virulence genes.

Item Type:Articles
Keywords:T3SS, inhibitor, EHEC, O157
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Roe, Professor Andrew
Authors: Tree, J.J., Wang, D., McInally, C., Mahajan, A., Layton, A., Houghton, I., Elofsson, M., Stevens, M.P., Gally, D.L., and Roe, A.J.
Subjects:Q Science > QR Microbiology > QR180 Immunology
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Infection and Immunity
Publisher:American Society for Microbiology
ISSN:0019-9567
ISSN (Online):1098-5522
Published Online:27 July 2009
Copyright Holders:Copyright © 2008 American Society for Microbiology
First Published:First published in Infection and Immunity 77(10):4209-4220
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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