title: The TolC protein of Legionella pneumophila plays a major role in multi-drug resistance and the early steps of host invasion.
abstract: Pneumonia associated with Iegionnaires's disease is initiated in humans after inhalation of contaminated aerosols. In the environment, Legionella pneumophila is thought to survive and multiply as an intracellular parasite within free-living amoeba. In the genome of L. pneumophila Lens, we identified a unique gene, tolC, encoding a protein that is highly homologous to the outer membrane protein TolC of Escherichia coli. Deletion of tolC by allelic exchange in L. pneumophila caused increased sensitivity to various drugs. The complementation of the tolC mutation in trans restored drug resistance, indicating that TolC is involved in multi-drug efflux machinery. In addition, deletion of tolC caused a significant attenuation of virulence towards both amoebae and macrophages. Thus, the TolC protein appears to play a crucial role in virulence which could be mediated by its involvement in efflux pump mechanisms. These findings will be helpful in unraveling the pathogenic mechanisms of L. pneumophila as well as in developing new therapeutic agents affecting the efflux of toxic compounds.
authors.affiliation: Université de Lyon, Lyon, France.
authors.forename: Mourad
authors.initials: M
authors.lastname: Ferhat
authors.forename: Danièle
authors.initials: D
authors.lastname: Atlan
authors.forename: Anne
authors.initials: A
authors.lastname: Vianney
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lazzaroni
authors.forename: Patricia
authors.initials: P
authors.lastname: Doublet
authors.forename: Christophe
authors.initials: C
authors.lastname: Gilbert
mesh_terms: D048248:Acanthamoeba castellanii / Q000382:microbiology; D000483:Alleles; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D018432:Drug Resistance, Multiple; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D006801:Humans; D016952:Legionella pneumophila / Q000378:metabolism* / Q000472:pathogenicity; D008826:Microbial Sensitivity Tests; D008957:Models, Genetic; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D017382:Reactive Oxygen Species; D020298:U937 Cells
chemical_list: D001425:Bacterial Outer Membrane Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017382:Reactive Oxygen Species; C548879:TolC protein, Legionella pneumophila