Eat in or Take out? Metabolism of Intracellular Salmonella enterica

Intracellular Salmonella enterica reside in the nutrient-poor, but replication-permissive Salmonella-containing vacuole (SCV). Here Salmonella relies on metabolic flexibility, as it is able to perform all major metabolic pathways. Which pathways are actually used shows striking cell-specific differences, illustrating the ability to adapt to specific environments. During SCV maturation, Salmonella induces formation of extensive and highly dynamic membrane tubules, that is, Salmonella-induced filaments (SIFs). These show after formation a unique conversion from single- to double-membrane structures, enlarging the volume of the SCV/SIF continuum substantially. The large SCV/SIF continuum is essential for efficient nutrition and thus for replication of intracellular Salmonella by interaction with the host endosomal system. It allows access to endosomal content and endocytosed nutrients. Salmonella enterica is an important gastrointestinal and facultative intracellular pathogen. After invasion of host cells, it resides in a specialized, replication-permissive compartment, the Salmonella-containing vacuole (SCV). During maturation of the SCV, Salmonella remodels the host endosomal system to form a variety of membranous extensions from the SCV, one type designated Salmonella-induced filaments (SIFs). It was long unclear how Salmonella is able to sustain replication within the SCV, thought to be a nutrient-poor environment. Recent studies started to characterize the metabolic pathways used by intracellular Salmonella. Besides, new insights into the ultrastructure and biogenesis of SIFs and their essential role in nutrition were obtained lately. Here, we review the recent progress with focus on observations gained by various cellular models. Salmonella enterica is an important gastrointestinal and facultative intracellular pathogen. After invasion of host cells, it resides in a specialized, replication-permissive compartment, the Salmonella-containing vacuole (SCV). During maturation of the SCV, Salmonella remodels the host endosomal system to form a variety of membranous extensions from the SCV, one type designated Salmonella-induced filaments (SIFs). It was long unclear how Salmonella is able to sustain replication within the SCV, thought to be a nutrient-poor environment. Recent studies started to characterize the metabolic pathways used by intracellular Salmonella. Besides, new insights into the ultrastructure and biogenesis of SIFs and their essential role in nutrition were obtained lately. Here, we review the recent progress with focus on observations gained by various cellular models. alternative metabolic pathways to prevent idling of intermediates originating from central pathways (e.g., the glyoxylate shunt for the TCA cycle). bacterial proteins translocated by their respective secretion system into the host cell fulfilling specific functions. a mass spectrometry- or nuclear magnetic resonance-based technique to characterize metabolic fluxes by identifying different species of a molecule by their differing molecular weight. nitrogen-containing radicals such as NO causing nitrosative stress. oxygen-containing radicals such as O2– or HO– causing oxidative stress. a membrane-bound intracellular compartment inhabited and manipulated by Salmonella to divert it from canonical phagosome maturation and to allow replication and characterized by late endosomal host proteins such as LAMP1 or RAB7. a highly dynamic SIT occurring late in SCV maturation with a corresponding membrane composition and forming double-membrane structures over time. a SIT occurring late in SCV maturation characterized by the trans-Golgi network host protein SCAMP3. the entirety of tubular/filamentous appendages of the SCV formed by manipulation of the host cell. over 20 distinct genomic regions in the chromosome of Salmonella initially acquired by horizontal gene transfer and encoding different virulence factors with SPI1 most important for invasion and SPI2 most important for intracellular lifestyle. distinct variations within a species or subspecies distinguished by typing serologically different surface structures. a SIT occurring early in SCV maturation characterized by the endosomal host protein SNX3. a SIT occurring early in SCV maturation characterized by the endosomal host protein SNX1. the transport of bacterial proteins into eukaryotic target cells. a machinery related to the flagellar apparatus for translocation of effector proteins into the host cytosol.