IntracellularSalmonellametabolism

Abstract

Growth of Salmonella inside infected host cells is a key aspect of their ability to cause local enteritis or systemic disease. This growth depends on exploitation of host nutrients through a large Salmonella metabolism network with hundreds of metabolites and enzymes. Studies in cell culture infection models are unravelling more and more of the underlying molecular and cellular mechanisms but also show striking Salmonella metabolic plasticity depending on host cell line and experimental conditions. In vivo studies have revealed a qualitatively diverse, but quantitatively poor, host-Salmonella nutritional interface, which on one side makes Salmonella fitness largely resilient against metabolic perturbations, but on the other side severely limits Salmonella biomass generation and growth rates. This review discusses goals and techniques for studying Salmonella intracellular metabolism, summarises main results and implications, and proposes key issues that could be addressed in future studies.

Immunometabolism at the interface between macrophages and pathogens

“…Typhimurium seems to be a 'generalist' with an extremely flexible metabolic capacity, such that few single mutations in metabolic pathways have a major effect on bacterial survival 27,28 .…”

Deletion of the lon gene augments expression of Salmonella Pathogenicity Island (SPI)-1 and metal ion uptake genes leading to the accumulation of bactericidal hydroxyl radicals and host pro-inflammatory cytokine-mediated rapid intracellular clearance

“…11,12 Further, Salmonella attempts to circumvent the recruitment of antigenpresenting cells to the site of infection by interacting with the host immune pathways 13 and exploits the metabolic pathways of the host for its survival. 14 Apart from manipulating these host mechanisms, the bacteria modulate their biosynthesis machinery that determines their fitness and virulence. 14,15 As a facultative anaerobe, Salmonella undergoes metabolic reprogramming depending on the presence or absence of oxygen.…”

“…14 Apart from manipulating these host mechanisms, the bacteria modulate their biosynthesis machinery that determines their fitness and virulence. 14,15 As a facultative anaerobe, Salmonella undergoes metabolic reprogramming depending on the presence or absence of oxygen. One of the principal determinants of this process is redox homeostasis.…”

CellularMicrobiology: The metabolic interface between host cell and pathogen

“…Transcriptional profiling, metabolomics, and transposon‐insertion site mapping screens and chemical screens against intracellular microbes have generated a rich body of literature demonstrating how microbial metabolism is impacted by the host cell environment. Some bacteria, such as Salmonella spp ., are generalists, show extensive metabolic flexibility, and can utilize a range of nutrients for anabolic and catabolic functions (Bumann & Schothorst, , Steeb et al, ). In contrast, other bacilli, such as Mycobacterium tuberculosis appear constrained by the intracellular environment and rely almost exclusively on host cell fatty acids and cholesterol (McKinney et al, , Nazarova et al, , Pandey & Sassetti, , VanderVen et al, ).…”