Autorepressor PsrA is required for optimal Legionella pneumophila growth in Acanthamoeba castellanii protozoa

Abstract

Legionella pneumophila is a facultative intracellular parasite of freshwater protozoa that undergoes a complex multiphasic lifecycle (Mondino et al., 2020;Newton et al., 2010). Two major morphological forms feature predominantly: a replicative rod-shaped form and a motile coccoid-shaped mature intracellular form (MIF) developed upon egress from the spent protozoan host (Garduño et al., 2002;Greub & Raoult, 2003;Robertson et al., 2014). This MIF (henceforth referred to as cyst form) features distinct ultrastructural characteristics (thickened cell wall, multilayer membrane laminations, poly-3-hydroxybutyrate [PHB] inclusions) ideal for long-term survival between protozoan hosts (Faulkner & Garduño, 2002). It is currently viewed that inhalation of aerosolized cyst-laden water droplets by a susceptible individual leads to infection of alveolar macrophages and manifestation of Legionnaires' disease.Successful infection of protozoa and macrophages by L. pneumophila is enabled by the Dot/Icm Type IV Secretion System (T4SS) which translocates >300 effector proteins into the host cell to manipulate diverse cellular processes (Burstein et al., 2016;Finsel & Hilbi, 2015;Gomez-Valero et al., 2019). In macrophages, the main targets include abrogation of the phagosome-lysosome fusion pathway and

Molecular regulation of virulence in Legionella pneumophila

“…A recent addition to the regulatory scheme is an ortholog of the Pseudomonas sigma regulator, PsrA (Graham et al, 2021).…”

“…L. pneumophila utilizes a complex regulatory network to sense its vation that a single cis encoded sRNA affects regulatory control (Graham et al, 2021;Saoud et al, 2021a).…”

“…A recent addition to the regulatory scheme is an ortholog of the Pseudomonas sigma regulator, PsrA (Graham et al., 2021). In Pseudomonas spp., the TetR family transcriptional regulator Pseudomonas PsrA (PsPsrA) acts as both an autorepressor and an important activator of rpoS expression (Kojic et al., 2002; Kojic & Venturi, 2001).…”

“…In L. pneumophila , a strong autoregulatory role was observed for PsrA but also deviated from the Pseudomonas paradigm in that PsrA did not regulate rpoS expression (Graham et al., 2021). Interestingly, PsrA was also demonstrated to have a role in the temporal progression of the L. pneumophila intracellular lifecycle in A. castellanii .…”

“…Interestingly, PsrA was also demonstrated to have a role in the temporal progression of the L. pneumophila intracellular lifecycle in A. castellanii . Elevated cellular levels of PsrA fostered larger than normal‐sized LCVs filled with replicative bacterial forms of which differentiation into MIFs was impeded (Graham et al., 2021). In efforts to define a PsrA regulon, transcriptomic studies showed an association with virulence and motility‐associated genes suggesting a link to the stringent response network, perhaps by regulating fatty acid metabolism via fadBA (Graham et al., 2021).…”