Title: Host succinate is an activation signal for Salmonella virulence during intracellular infection

Author: Gili Rosenberg, Dror Yehezkel, Dotan Hoffman, Camilla Ciolli Mattioli, Moran Fremder, Hadar Ben-Arosh, Leia Vainman, Noa Nissani, Shelly Hen-Avivi, Shirley Brenner, Maxim Itkin, Sergey Malitsky, Ehud Ohana, Noa Bossel Ben-Moshe, Roi Avraham

Issue&Volume: 2021/01/22

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.

DOI: 10.1126/science.aba8026

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