title: Targeting bacterial virulence: inhibitors of type III secretion in Yersinia.
abstract: Agents that target bacterial virulence without detrimental effect on bacterial growth are useful chemical probes for studies of virulence and potential candidates for drug development. Several gram-negative pathogens employ type III secretion to evade the innate immune response of the host. Screening of a chemical library with a luciferase reporter gene assay in viable Yersinia pseudotuberculosis furnished several compounds that inhibit the reporter gene signal expressed from the yopE promoter and effector protein secretion at concentrations with no or modest effect on bacterial growth. The selectivity patterns observed for inhibition of various reporter gene strains indicate that the compounds target the type III secretion machinery at different levels. Identification of this set of inhibitors illustrates the approach of utilizing cell-based assays to identify compounds that affect complex bacterial virulence systems.
authors.affiliation: Organic Chemistry, Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Kauppi
authors.forename: Roland
authors.initials: R
authors.lastname: Nordfelth
authors.forename: Hanna
authors.initials: H
authors.lastname: Uvell
authors.forename: Hans
authors.initials: H
authors.lastname: Wolf-Watz
authors.forename: Mikael
authors.initials: M
authors.lastname: Elofsson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D001681:Biological Assay; D015153:Blotting, Western; D016503:Drug Delivery Systems; D017930:Genes, Reporter; D011401:Promoter Regions, Genetic; D014774:Virulence; D015011:Yersinia pseudotuberculosis / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; C063239:yopE protein, Yersinia