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Infection and Immunity, October 2009, p. 4209-4220, Vol. 77, No. 10
0019-9567/09/$08.00+0 doi:10.1128/IAI.00562-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Characterization of the Effects of Salicylidene Acylhydrazide Compounds on Type III Secretion in Escherichia coli O157:H7 
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Jai J. Tree,1
Dai Wang,2
Carol McInally,2
Arvind Mahajan,3
Abigail Layton,4
Irene Houghton,2
Mikael Elofsson,5
Mark P. Stevens,4
David L. Gally,1 and
Andrew J. Roe2*
Zoonotic and Animal Pathogens Research Laboratory, Immunity and Infection Division, The Roslin Institute and Royal (Dick) School of Veterinary Studies, Chancellor's Building, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom,1 Microbiology Research Group, Infection and Immunity, Glasgow Biomedical Research Centre, Faculty of Biomedical & Life Sciences, Glasgow G12 8QQ, United Kingdom,2 Cellular Microbiology Group, Division of Infection and Immunity, The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Penicuik EH25 9RG, United Kingdom,3 Division of Microbiology, Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, United Kingdom,4 Department of Chemistry, Umea University, SE-90187 Umea, Sweden5
Received 20 May 2009/ Returned for modification 24 June 2009/ Accepted 16 July 2009
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 Escherichia coli O157:H7 in liquid culture and when this bacterium is attached to bovine epithelial cells. Inhibition of T3SS expression resulted in a reduction in the capacity of the bacteria to form attaching and effacing lesions. Our results show that there is marked variation in the abilities of four structurally related compounds to inhibit the T3SS of a panel of isolates. Using transcriptomics, we performed a comprehensive analysis of the conserved and inhibitor-specific transcriptional responses to these 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 for the different compounds. Overall, we highlight the importance of assessing the effect of such "antivirulence" agents on a range of isolates and discuss the possible mechanisms which may lead to the coordinate downregulation of horizontally acquired virulence genes.
* Corresponding author. Mailing address: Microbiology Research Group, Infection and Immunity, Glasgow Biomedical Research Centre, Faculty of Biomedical & Life Sciences, Glasgow G12 8QQ, United Kingdom. Phone: 44 141 3302980. Fax: 44 141 3304600. E-mail: andrew.roe{at}bio.gla.ac.uk
Published ahead of print on 27 July 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
Infection and Immunity, October 2009, p. 4209-4220, Vol. 77, No. 10
0019-9567/09/$08.00+0 doi:10.1128/IAI.00562-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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