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.

Methionine is a nutritionally essential sulfur-containing amino acid found at low levels in plant tissues. Yet, the factors that regulate its synthesis and accumulation in seeds are not fully known. Recent genetic studies demonstrate that Arabidopsis seeds are able to synthesize methionine de novo through the aspartate family pathway similarly to vegetative tissues; however, additional biochemical studies suggest that the S-methylmethionine (SMM) cycle also plays a major role in methionine synthesis in seeds. To better understand the contribution of these two pathways to methionine synthesis, we have sampled various vegetative and reproductive tissues during the Arabidopsis life cycle and determined the contents of soluble and protein-incorporated methionine, SMM, as well as the expression levels of the key genes involved in these two pathways. Our results strengthen the hypothesis that SMM that is produced in the rosette leaves from methionine contributes to methionine accumulation in seeds. However, the SMM cycle may have additional functions in plant tissues since its key genes were expressed in all of the examined tissues, although at different rates. The accumulation patterns of soluble and protein-incorporated methionine during the Arabidopsis life cycle were found to be similar to most of the other amino acids, especially to those belonging to the branched-chain and aromatic amino acids that are produced in chloroplasts together with methionine. This indicates that similar factors regulate the levels of amino acids during development.

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Summary Interactions between intracellular bacteria and mononuclear phagocytes give rise to diverse cellular phenotypes that may determine the outcome of infection. Recent advances in single-cell RNA sequencing (scRNA-seq) have identified multiple subsets within the mononuclear population, but implications to their function during infection are limited. Here, we surveyed the mononuclear niche of intracellular Salmonella Typhimurium ( S .Tm) during early systemic infection in mice. We described eclipse-like growth kinetics in the spleen, with a first phase of bacterial control mediated by tissue-resident red-pulp macrophages. A second phase involved extensive bacterial replication within a macrophage population characterized by CD9 expression. We demonstrated that CD9 + macrophages induced pathways for detoxificating oxidized lipids, that may be utilized by intracellular S .Tm. We established that CD9 + macrophages originated from non-classical monocytes (NCM), and NCM-depleted mice were more resistant to S .Tm infection. Our study defines macrophage subset-specific host-pathogen interactions that determine early infection dynamics and infection outcome of the entire organism.