The infectious intracellular lifestyle ofSalmonella entericarelies on the adaptation to nutritional conditions within theSalmonella-containing vacuole

Abstract

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative pathogen that causes various host-specific diseases. During their life cycle, Salmonellae survive frequent exposures to a variety of environmental stresses, e.g. carbon-source starvation. The virulence of this pathogen relies on its ability to establish a replicative niche, named Salmonella-containing vacuole, inside host cells. However, the microenvironment of the SCV and the bacterial metabolic pathways required during infection are largely undefined. In this work we developed different biological probes whose expression is modulated by the environment and the physiological state of the bacterium. We constructed transcriptional reporters by fusing promoter regions to the gfpmut3a gene to monitor the expression profile of genes involved in glucose utilization and lipid catabolism. The induction of these probes by a specific metabolic change was first tested in vitro, and then during different conditions of infection in macrophages. We were able to determine that Entner-Doudoroff is the main metabolic pathway utilized by Salmonella during infection in mouse macrophages. Furthermore, we found sub-populations of bacteria expressing genes involved in pathways for the utilization of different sources of carbon. These populations are modified in presence of different metabolizable substrates, suggesting the coexistence of Salmonella with diverse metabolic states during the infection.

IntracellularSalmonellametabolism

“…Most previous investigations have determined average properties, but recent studies clearly revealed striking differences between individual Salmonella cells but also substantial cell‐to‐cell variation among host cells. Salmonella subsets with divergent growth rates and metabolic activities exist in infected macrophages (Claudi et al, ; Diacovich, Lorenzi, Tomassetti, Meresse, & Gramajo, ; Helaine et al, ; Helaine, Cheverton, et al, ), and properties and fates of individual Salmonella ‐infected macrophages are also highly variable (Avraham et al, ; McQuate et al, ; Saliba et al, ; Thurston et al, ). Striking heterogeneity has also been observed in epithelial HeLa cells.…”

Genome‐scale metabolic reconstruction and in silico analysis of the rice leaf blight pathogen, Xanthomonas oryzae

“…We found that all genera have strains encoding the ED pathway (Tables and ). It is also important to note that this pathway has been reported to have close association with the virulence of several mammalian bacterial pathogens (Patra et al , ; Diacovich et al , ), suggesting that the ED pathway might be a more common feature of gram‐negative bacterial pathogens infecting animal and plant hosts than previously thought. Another important observation is that although EC numbers are fairly similar among the three pathogens, Xoo has significantly fewer genes in oxidative phosphorylation and pyruvate metabolisms, possibly indicating the relatively lower importance of these pathways for its survival in the rice xylem niche compared to the other two.…”

Therapeutic lipid-coated hybrid nanoparticles against bacterial infections

“…7A). 112 However, certain intracellular bacterial pathogens, such as Mycobacterium tuberculosis, 113,114 Salmonella enterica, 115 and Klebsiella pneumoniae, 116 develop various defence mechanisms to escape the phagocytosis pathways or remain viable in the phagolysosomes, which is the case for infectious diseases, such as tuberculosis, 117 listeriosis, 118 and salmonellosis. 119 Recent research demonstrated that Klebsiella pneumoniae can promote the activation of Akt to arrest phagosome maturation, avoiding fusion into lysosomes, thus creating a Klebsiella-containing vacuole to survival intracellularly (Fig.…”