Host succinate is an activation signal for Salmonella virulence during intracellular infection Gili Rosenburg et al, 2021

Mij · Jan 22, 2021

Salmonella profits from immunometabolism
Extensive metabolic rewiring occurs in various immune cells during the course of infection. Whether these changes can be exploited by intracellular pathogens remains an open question. Rosenberg et al. report that infection with Salmonella enterica serovar Typhimurium (S. Tm) induces the accumulation of the metabolite succinate in macrophages (see the Perspective by Lynch and Lesser). This key intermediate in the citric acid cycle activates virulence genes in S. Tm, leading to microbial resistance. Moreover, the active transport of succinate through the C4-dicarboxylate transporter DcuB is required for S. Tm virulence and survival within macrophages. Sensing of citric acid cycle intermediates may more generally serve as a cue to initiate the resistance of programs of intracellular pathogens.
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Abstract
Key to the success of intracellular pathogens is the ability to sense and respond to a changing host cell environment. Macrophages exposed to microbial products undergo metabolic changes that drive inflammatory responses. However, the role of macrophage metabolic reprogramming in bacterial adaptation to the intracellular environment has not been explored. Here, using metabolic profiling and dual RNA sequencing, we show that succinate accumulation in macrophages is sensed by intracellular Salmonella Typhimurium (S. Tm) to promote antimicrobial resistance and type III secretion. S. Tm lacking the succinate uptake transporter DcuB displays impaired survival in macrophages and in mice. Thus, S. Tm co-opts the metabolic reprogramming of infected macrophages as a signal that induces its own virulence and survival, providing an additional perspective on metabolic host–pathogen cross-talk.
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How massive metabolic changes immunometabolism affect intracellular bacteria?

https://science.sciencemag.org/content/371/6527/400

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Host succinate is an activation signal for Salmonella virulence during intracellular infection Gili Rosenburg et al, 2021

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Host succinate is an activation signal for Salmonella virulence during intracellular infection Gili Rosenburg et al, 2021

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