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 legionnaires'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, toIC, encoding a protein that is highly homologous to the outer membrane protein ToIC of Escherichia coli. Deletion of toIC by allelic exchange in L. pneumophila caused increased sensitivity to various drugs. The complementation of the toIC mutation in trans restored drug resistance, indicating that ToIC is involved in multi-drug efflux machinery. In addition, deletion of toIC caused a significant attenuation of virulence towards both amoebae and macrophages. Thus, the ToIC 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. © 2009 Ferhat et al.