title: The starvation-stress response (SSR) of Salmonella.
abstract: Salmonella serovars are common etiologic agents of intestinal-based disease of animals and humans. As a result of their lifestyle, salmonellae occupy and survive in a wide range of niches where they can encounter an even broader range of environmental stresses. One of the most common stresses is starvation for an essential nutrient such as a carbon/energy (C)-source. The genetic and physiologic changes that the bacterium undergoes in response to starvation-stress are referred to as the starvation-stress response or SSR. The genetic loci whose expression increases in response to the starvation-stress compose the SSR stimulon. Several loci of the SSR stimulon have been identified in Salmonella typhimurium and grouped, based on putative or known functions or products, into transport systems, C-compound catabolic enzymes, known protective enzymes, respiratory enzyme systems, regulatory proteins, virulence loci and unclassified products. The majority of loci identified are under positive control by the rpoS-encoded sigma factor, sigma S. However, a few are under (indirect) negative control by sigma S, but only during starvation-induced stationary phase. Most of the loci identified are also under either positive or negative control by the cAMP:CRP complex. For many, additional regulatory proteins (e.g. FadR, OxyR, and RelA and others) play a role in their regulation as well. Furthermore, most of the SSR loci identified are induced during other stresses or environmental conditions. For example, some are induced during P- or N-starvation, in addition to C-starvation; some are induced by extremes in pH or osmolarity; and some are induced in the intracellular environment of epithelial cells, and/or macrophages, and/or medium designed to mimic the intracellular milieu of mammalian cells (ISM). Several SSR loci are required for long-term starvation-survival (core SSR loci), e.g. narZ, dadA, stiC and rpoS. In addition, a few of the core SSR loci are also required for stress-specific-inducible and/or C-starvation-inducible resistance to H2O2 (e.g. stiC), thermal (e.g. stiC), and/or acid pH (e.g. narZ), challenge. Interestingly, C-starved cells are resistant to challenge with the antimicrobial peptide, polymyxin B. However, this resistance mechanism(s) is different from the resistance mechanisms for H2O2 and other environmental stresses. Furthermore, a link between the SSR and Salmonella virulence can be hypothesized since the two major regulators of the SSR, sigma s and cAMP:CRP, are required for full virulence of Salmonella. Moreover, the spv (Salmonella plasmid-associated virulence) genes, required for Salmonella to cause systemic disease, are C (and P- and N-)-starvation-inducible. However, a direct link between starvation-stress and virulence has not been established conclusively.
authors.affiliation: Department of Biomedical Sciences, University of South Alabama, Mobile 36688, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Spector
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D015964:Gene Expression Regulation, Bacterial; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D011112:Polymyxin B / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000502:physiology*; D012808:Sigma Factor
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D012808:Sigma Factor; D006861:Hydrogen Peroxide; D011112:Polymyxin B