A stress-induced block in dicarboxylate uptake and utilization in Salmonella

Abstract

14Bacteria have evolved to sense and respond to their environment by altering gene 15 expression and metabolism to promote growth and survival. In this work we demonstrate a novel 16 phenotype wherein Salmonella actively represses its growth when using dicarboxylates such as 17 succinate as the sole carbon source. This repression is mediated by RpoS, the RssB anti-adaptor 18IraP, and to a lesser degree the stringent response. We also show that small amounts of proline or 19 citrate can act as inducers of growth in succinate media. Ultimately this regulatory cascade 20 represses dctA, encoding the primary dicarboxylate importer, and constitutive expression of dctA 21 induced growth. Additionally, we show that this phenotype diverges between Salmonella and its 22Importance 31Bacteria have evolved to sense and respond to their environment to maximize their 32 chance of survival. By studying differences in the responses of pathogenic bacteria and closely 33 related non-pathogens, we can gain insight into what environments they encounter inside of an 34 infected host. Here we demonstrate that Salmonella diverges from its close relative E. coli in its 35 response to the metabolite succinate and other dicarboxylates. We show that this is regulated by 36 stress response proteins and ultimately can be attributed to Salmonella repressing its import of 37 dicarboxylates. Though this exclusion of dicarboxylates did not influence Salmonella's survival 38 in macrophage, we propose other advantages that this trait may provide Salmonella within an 39 infected host. Understanding this phenomenon may reveal a novel aspect of the Salmonella 40 virulence cycle, and our charcterization of its regulation yields a number of mutant strains that 41can be used to further study it. 42