title: The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a role in pathogenesis.
abstract: The ability of an isogenic set of mutants of Salmonella enterica serovar Typhimurium L354 (SL1344) with defined deletions in genes encoding components of tripartite efflux pumps, including acrB, acrD, acrF and tolC, to colonize chickens was determined in competition with L354. In addition, the ability of L354 and each mutant to adhere to, and invade, human embryonic intestine cells and mouse monocyte macrophages was determined in vitro. The tolC and acrB knockout mutants were hyper-susceptible to a range of antibiotics, dyes and detergents; the tolC mutant was also more susceptible to acid pH and bile and grew more slowly than L354. Complementation of either gene ablated the phenotype. The tolC mutant poorly adhered to both cell types in vitro and was unable to invade macrophages. The acrB mutant adhered, but did not invade macrophages. In vivo, both the acrB mutant and the tolC mutant colonized poorly and did not persist in the avian gut, whereas the acrD and acrF mutant colonized and persisted as well as L354. These data indicate that the AcrAB-TolC system is important for the colonization of chickens by S. Typhimurium and that this system has a role in mediating adherence and uptake into target host cells.
authors.affiliation: Antimicrobial Agents Research Group, Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Buckley
authors.forename: Mark A
authors.initials: MA
authors.lastname: Webber
authors.forename: Sue
authors.initials: S
authors.lastname: Cooles
authors.forename: Luke P
authors.initials: LP
authors.lastname: Randall
authors.forename: Roberto M
authors.initials: RM
authors.lastname: La Ragione
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Woodward
authors.forename: Laura J V
authors.initials: LJ
authors.lastname: Piddock
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001715:Bird Diseases / Q000382:microbiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D041981:Gastrointestinal Tract / Q000382:microbiology / Q000648:ultrastructure; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D051379:Mice; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D009154:Mutation; D012481:Salmonella Infections, Animal / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: C493251:AcrAB-TolC protein, Salmonella enterica; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins