Nutrient salvaging and metabolism by the intracellular pathogen Legionella pneumophila

Abstract

The Gram-negative bacterium Legionella pneumophila is ubiquitous in freshwater environments as a free-swimming organism, resident of biofilms, or parasite of protozoa. If the bacterium is aerosolized and inhaled by a susceptible human host, it can infect alveolar macrophages and cause a severe pneumonia known as Legionnaires' disease. A sophisticated cell differentiation program equips L. pneumophila to persist in both extracellular and intracellular niches. During its life cycle, L. pneumophila alternates between at least two distinct forms: a transmissive form equipped to infect host cells and evade lysosomal degradation, and a replicative form that multiplies within a phagosomal compartment that it has retooled to its advantage. The efficient changeover between transmissive and replicative states is fundamental to L. pneumophila's fitness as an intracellular pathogen. The transmission and replication programs of L. pneumophila are governed by a number of metabolic cues that signal whether conditions are favorable for replication or instead trigger escape from a spent host. Several lines of experimental evidence gathered over the past decade establish strong links between metabolism, cellular differentiation, and virulence of L. pneumophila. Herein, we focus on current knowledge of the metabolic components employed by intracellular L. pneumophila for cell differentiation, nutrient salvaging and utilization of host factors. Specifically, we highlight the metabolic cues that are coupled to bacterial differentiation, nutrient acquisition systems, and the strategies utilized by L. pneumophila to exploit host metabolites for intracellular replication.

Growth-related Metabolism of the Carbon Storage Poly-3-hydroxybutyrate in Legionella pneumophila

“…Following this feature, the synthesis of PHB is also induced during the PE phase. In line with earlier observations (15), glucose may therefore be an important additional substrate under intracellular conditions to feed the biosynthesis of PHB when the bacteria become virulent, leave the vacuoles, and meet new substrates such as glucose in the cytosolic compartment of the host cell (20,52). Notably, glucose could also be generated from cytosolic glycogen of the host cells by the action of the bacterial glycogendegrading enzyme GamA (34).…”

“…However, it cannot be excluded that glucose (or sugars in general) is also incorporated into carbohydrates and cell wall components of L. pneumophila because these products were not analyzed in our study. Remarkably, the role of gluconeogenesis for the metabolism of L. pneumophila is still unclear (16,20).…”

“…Mainly on the basis of genome sequencing and studies under in vitro conditions, the core metabolic capabilities of L. pneumophila appear to be known (20). It is now established knowledge that amino acids, e.g.…”

“…It has been repeatedly reported that glucose is not a major carbon substrate of L. pneumophila (16,30,31), although genome analyses revealed the presence of the Embden-Meyerhof-Parnas pathway and the Entner-Doudoroff (ED) pathway (16,20,32). More recently, 13 C labeling experiments under in vitro conditions demonstrated that exogenous glucose can indeed be utilized through the ED pathway, finally providing pyruvate, oxaloacetate, and ␣-ketoglutarate as precursors for some amino acids and acetyl-CoA for PHB biosynthesis (19) (Fig.…”

“…1). Amino acids also play an important role as nutrients during growth within host cells (14,20,(27)(28)(29).…”