The life stage‐specific pathometabolism of Legionella pneumophila

Abstract

The genus Legionella belongs to Gram-negative bacteria found ubiquitously in aquatic habitats, where it grows in natural biofilms and replicates intracellularly in various protozoa (amoebae, ciliates). L. pneumophila is known as the causative agent of Legionnaires' disease, since it is also able to replicate in human alveolar macrophages, finally leading to inflammation of the lung and pneumonia. To withstand the degradation by its host cells, a Legionellacontaining vacuole (LCV) is established for intracellular replication, and numerous effector proteins are secreted into the host cytosol using a type four B secretion system (T4BSS). During intracellular replication, Legionella has a biphasic developmental cycle that alternates between a replicative and a transmissive form. New knowledge about the host-adapted and life stagedependent metabolism of intracellular L. pneumophila revealed a bipartite metabolic network with life stage-specific usages of amino acids (e.g. serine), carbohydrates (e.g. glucose) and glycerol as major substrates. These metabolic features are associated with the differentiation of the intracellular bacteria, and thus have an important impact on the virulence of L. pneumophila.

Biphasic Metabolism and Host Interaction of a Chlamydial Symbiont

“…Intracellular growth of L. pneumophila within A. castellanii requires amino acids as energy source and—similarly to our model for Protochlamydia —as the carbon source and directly for protein biosynthesis (72, 73). Although a temporal separation of amino acid and carbohydrate usage has not yet been shown in vivo for L. pneumophila , a pronounced transcriptional switch between replicative and transmissive phase within A. castellanii has been reported (74).…”

Branching Out: Alterations in Bacterial Physiology and Virulence Due to Branched-Chain Amino Acid Deprivation

“…Yet, some intracellular pathogens are auxotrophic for BCAAs and therefore necessitate transporters to obtain BCAAs. The BCAA auxotroph Legionella pneumophila requires the Val transporter PhtJ for intracellular growth (115, 141), and pathogenic subspecies of Francisella , which have lost the capacity to synthesize BCAAs, require the Ile transporter IleP for intracellular replication and infection in vivo (114). Interestingly, F.…”

Differential Substrate Usage and Metabolic Fluxes in Francisella tularensis Subspecies holarctica and Francisella novicida

“…This was strongly supported by a report showing that the SLC family of host amino acid transporters is important for intracellular replication of Fth strain LVS (Barel et al, 2012). Interestingly, although Fth replicates in the cytosol, a similar finding of the usage of amino acids during intracellular growth and the involvement of SLC proteins of the host cell was found for L. pneumophila , a human pathogenic bacterium which replicates within a vacuole in alveolar macrophages (Wieland et al, 2005; Eisenreich and Heuner, 2016). …”

“…To efficiently utilize carbon substrates from the cytosolic compartment of the host cell, L. monocytogenes has been shown to take advantage from multiple substrates (e.g., glucose phosphate, glycerol and amino acids) which are shuffled in a bipartite metabolic network to serve specific metabolic traits (Grubmüller et al, 2014). Multiple substrate usage might be a general strategy for intracellular bacteria growing in the cytosol, but also in phagosomal compartments (Abu Kwaik and Bumann, 2013, 2015; Schunder et al, 2014; Eisenreich and Heuner, 2016; Gillmaier et al, 2016; Häuslein et al, 2016). …”