title: Characterization of the effects of salicylidene acylhydrazide compounds on type III secretion in Escherichia coli O157:H7.
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 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.
authors.affiliation: Zoonotic and Animal Pathogens Research Laboratory, Immunity and Infection Division, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom.
authors.forename: Jai J
authors.initials: JJ
authors.lastname: Tree
authors.forename: Dai
authors.initials: D
authors.lastname: Wang
authors.forename: Carol
authors.initials: C
authors.lastname: McInally
authors.forename: Arvind
authors.initials: A
authors.lastname: Mahajan
authors.forename: Abigail
authors.initials: A
authors.lastname: Layton
authors.forename: Irene
authors.initials: I
authors.lastname: Houghton
authors.forename: Mikael
authors.initials: M
authors.lastname: Elofsson
authors.forename: Mark P
authors.initials: MP
authors.lastname: Stevens
authors.forename: David L
authors.initials: DL
authors.lastname: Gally
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Roe
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion; D002417:Cattle; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology; D019453:Escherichia coli O157 / Q000187:drug effects*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006834:Hydrazines / Q000494:pharmacology*; D015394:Molecular Structure; D010636:Phenols / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D021381:Protein Transport / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D006834:Hydrazines; D010636:Phenols