Role of Ubiquitin in the Survival of Legionella pneumophila in Eukaryotic Host Cells

Abstract

Background: Eukaryotic cells use essential ubiquitin-mediated pathways in their defense against pathogenic bacteria, such as Legionella pneumophila, the intracellular pathogen of Legionnaire’s disease. Despite the protective role of these pathways, L. pneumophila virulence has evolved to secrete numerous effector proteins involved in co-opting host ubiquitin-mediated processes to facilitate their survival. Many of these effector proteins are of great research interest in the quest to demystify the molecular mechanisms underlying L. pneumophila pathogenesis as the bacterium has a vast repertoire of effector proteins. Methods: Articles were obtained from scientific literature databases such as PubMed and the McGill library. Selected articles provided an overview of the ubiquitination pathway, eukaryotic autophagy, L. pneumophila pathogenesis, and structural and functional analysis of L. pneumophila and other bacterial effectors involved in subverting host ubiquitin systems. Summary: This review discusses the current structural and functional characterization of L. pneumophila protein effectors involved in exploiting host ubiquitin machinery to facilitate intracellular bacterial survival. These protein effectors include those with E3 ubiquitin ligase activity, LubX, AnkB, and SidC, which respectively mediate bacterial nutrient acquisition, temporal regulation of other effectors, and remodelling of the L. pneumophila replicative niche; the SidE family of effectors, which mediates the first novel, single-enzyme ubiquitination pathway and deubiquitination; and ravZ, a protease promoting evasion of host autophagy. However, the exact molecular functions and biological consequences of these effectors as well as the full repertoire of L. pneumophila effectors facilitating ubiquitin-mediated survival still require further investigation.