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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.

The TolC Protein of Legionella pneumophila Plays a Major Role in Multi-Drug Resistance and the Early Steps of Host Invasion