1887

Abstract

The starvation-stress response (SSR) of includes gene products necessary for starvation avoidance, starvation survival and virulence for this bacterium. Numerous genetic loci induced during carbon-source starvation and required for the long-term-starvation survival of this bacterium have been identified. The SSR not only protects the cell against the adverse effects of long-term starvation but also provides cross-resistance to other environmental stresses, e.g. thermal challenge (55 °C) or acid-pH challenge (pH 28). One carbon-starvation-inducible fusion, designated was previously reported to be a σ-dependent SSR locus that is phosphate-starvation, nitrogen-starvation and HO inducible, positively regulated by (p)ppGpp in a -dependent manner, and negatively regulated by cAMP:cAMP receptor protein complex and OxyR. We have discovered through sequence analysis and subsequent biochemical analysis that the :: fusion, and a similarly regulated fusion designated , lie at separate sites within the first gene () of an operon encoding a cryptic nitrate reductase () of unknown physiological function. In this study, it was demonstrated that was negatively regulated by the global regulator Fnr during anaerobiosis. Interestingly, ) was required for carbon-starvation-inducible thermotolerance and acid tolerance. In addition, expression was induced ∼20-fold intracellularly in Madin-Darby canine kidney epithelial cells and ∼16-fold in intracellular salts medium, which is believed to mimic the intracellular milieu. Also, a knock-out mutation increased the LD ∼10-fold for SL1344 delivered orally in the mouse virulence model. Thus, the previously believed cryptic and constitutive operon is in fact highly regulated by a complex network of environmental-stress signals and global regulatory functions, indicating a central role in the physiology of starved and stressed cells.

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1999-11-01
2024-04-24
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