The Flagellar Regulon of Legionella—A Review

Abstract

The Legionella genus comprises more than 60 species. In particular, Legionella pneumophila is known to cause severe illnesses in humans. Legionellaceae are ubiquitous inhabitants of aquatic environments. Some Legionellaceae are motile and their motility is important to move around in habitats. Motility can be considered as a potential virulence factor as already shown for various human pathogens. The genes of the flagellar system, regulator and structural genes, are structured in hierarchical levels described as the flagellar regulon. Their expression is modulated by various environmental factors. For L. pneumophila it was shown that the expression of genes of the flagellar regulon is modulated by the actual growth phase and temperature. Especially, flagellated Legionella are known to express genes during the transmissive phase of growth that are involved in the expression of virulence traits. It has been demonstrated that the alternative sigma-28 factor is part of the link between virulence expression and motility. In the following review, the structure of the flagellar regulon of L. pneumophila is discussed and compared to other flagellar systems of different Legionella species. Recently, it has been described that Legionella micdadei and Legionella fallonii contain a second putative partial flagellar system. Hence, the report will focus on flagellated and non-flagellated Legionella strains, phylogenetic relationships, the role and function of the alternative sigma factor (FliA) and its anti-sigma-28 factor (FlgM).

A Two-Component System that Modulates Cyclic-di-GMP Metabolism PromotesLegionella pneumophilaDifferentiation and Viability in Low-Nutrient Conditions

“…2), we postulated that transcription of lpg0279-77 and flaA may be controlled by the same regulatory proteins. Therefore, we assessed the contribution of a subset of the regulators known to coordinate the L. pneumophila transition from E to PE phase (16, 30–33). To do this, the p lpg0279-gfp and p flaA-gfp reporters were transformed into mutants lacking either the alternative sigma factors FliA (σ 28 ) or RpoS (σ S /σ 38 ), the two-component system LetA/S, or the ppGpp synthetase RelA.…”

Stable sub-complexes observedin situsuggest a modular assembly pathway of the bacterial flagellar motor

“…We recently reported the structure of the intact flagellar motor in three non-enteric Gammaproteobacteria species, Legionella pneumophila , Pseudomonas aeruginosa and Shewanella oneidensis MR-1 by ECT 30 . L. pneumophila and P. aeruginosa are human pathogens that cause serious pulmonary infections in which the flagellum is a key virulence factor 31,32 . S. oneidensis is a model system for studying extracellular respiration and is known for its production of multiheme cytochrome electron conduits and outer-membrane appendages 33 .…”

Evasion of phagotrophic predation by protist hosts and innate immunity of metazoan hosts byLegionella pneumophila

“…NLRC4 (also known as Ipaf) interacts with Naip5 and recognizes L. pneumophila flagellin, leading to the NLRC4-Naip5 inflammasome, activation of caspase-1, −7 and −11, and delivery of L. pneumophila to the lysosome (A. Amer et al, 2006; Appelt & Heuner, 2017; Casson & Shin, 2013; Jörn Coers, Vance, Fontana, & Dietrich, 2007; Halff et al, 2012; He & Amer, 2014; M. Lamkanfi et al, 2007; Lamkanfi, Kanneganti, Franchi, & Núñez, 2007; Lightfield et al, 2008; Molofsky et al, 2006; Speir et al, 2017).…”

“…and delivery of L. pneumophila to the lysosome (A. Amer et al, 2006;Appelt & Heuner, 2017;Casson & Shin, 2013;Coers, Vance, Fontana, & Dietrich, 2007;Halff et al, 2012;He & Amer, 2014;Lamkanfi, Amer, et al, 2007;Lamkanfi, Kanneganti, Franchi, & Núñez, 2007;Lightfield et al, 2008;Molofsky et al, 2006;Speir et al, 2017). However, in human macrophages and the permissive A/J mouse strain, the Naip5 allele is defective in detecting L. pneumophila flagellin; thus, caspase-1, caspase-7, and caspase-11 are not activated, allowing for robust intracellular replication (Figure 1; Akhter et al, 2009Akhter et al, , 2012A.…”