title: Salicylidene acylhydrazide-mediated inhibition of type III secretion system-1 in Salmonella enterica serovar Typhimurium is associated with iron restriction and can be reversed by free iron.
abstract: Salmonella enterica serovar Typhimurium is an animal and zoonotic pathogen of worldwide importance. Intestinal colonization, induction of enteritis and systemic translocation by this bacterium requires type III protein secretion. Strategies that target this process have the potential to control infection, pathology and transmission. We defined the global transcriptional response of S. Typhimurium to INP0403, a member of a family of salicylidene acylhydrazides that inhibit type III secretion (T3S). INP0403 treatment was associated with reduced transcription of genes involved in T3S, but also increased transcription of genes associated with iron acquisition. We show that INP0403 restricts iron availability to Salmonella, and that inhibition of T3S system-1 by INP0403 is, at least in part, reversible by exogenous iron and independent of the iron response regulator Fur.
authors.affiliation: Division of Microbiology, Institute for Animal Health, Compton, Berkshire, UK. abigail.layton@bbsrc.ac.uk
authors.forename: Abigail N
authors.initials: AN
authors.lastname: Layton
authors.forename: Debra L
authors.initials: DL
authors.lastname: Hudson
authors.forename: Arthur
authors.initials: A
authors.lastname: Thompson
authors.forename: Jay C D
authors.initials: JC
authors.lastname: Hinton
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Stevens
authors.forename: Edouard E
authors.initials: EE
authors.lastname: Galyov
authors.forename: Mark P
authors.initials: MP
authors.lastname: Stevens
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D026901:Membrane Transport Proteins; D049452:Green Fluorescent Proteins; D007501:Iron