bioRxiv | 2019
Salmonella stress response mediates growth repression in succinate media
Abstract
Abstract Bacteria have evolved to sense and respond to their environment by altering gene expression and metabolism to promote growth and survival. In this work we demonstrate a novel phenotype wherein Salmonella actively represses its growth when using dicarboxylates such as succinate as the sole carbon source. This repression is mediated by RpoS, the RssB anti-adaptor IraP, and to a lesser degree the stringent response. We also show that small amounts of proline or citrate can act as inducers of growth in succinate media. Ultimately this regulatory cascade represses dctA, encoding the primary dicarboxylate importer, and constitutive expression of dctA induced growth. Additionally, we show that this phenotype diverges between Salmonella and its close relative E. coli, and replacing the Salmonella dctA promoter with that of E. coli was sufficient to abolish growth repression. We hypothesized that this divergence might reflect an adaptation to Salmonella’s virulent lifestyle including survival in macrophage where levels of succinate increase in response to bacterial LPS. We found that impairing dctA repression had no effect on Salmonella’s survival in acidified succinate or in macrophage but propose alternate hypotheses of fitness advantages acquired by repressing dicarboxylate uptake. In summary we identify a novel Salmonella phenotype and insight into its regulation. This phenotype is divergent from E. coli and may represent an adaptation to Salmonella’s virulent lifestyle. Importance Bacteria have evolved to sense and respond to their environment to maximize their chance of survival. By studying differences in the responses of pathogenic bacteria and closely related non-pathogens, we can gain insight into what environments they encounter inside of an infected host. Here we demonstrate that Salmonella diverges from its close relative E. coli in its response to the metabolite succinate and other dicarboxylates. We show that this is regulated by stress response proteins and ultimately can be attributed to Salmonella repressing its import of dicarboxylates. Though this exclusion of dicarboxylates did not influence Salmonella’s survival in macrophage, we propose other advantages that this trait may provide Salmonella within an infected host. Understanding this phenomenon may reveal a novel aspect of the Salmonella virulence cycle, and our charcterization of its regulation yields a number of mutant strains that can be used to further study it.