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)

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 > School of Infection & Immunity
• 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.