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When life poses challenges, bacteria are quick to counter with adaptive responses to chemical and physical stresses. Alternative sigma subunits of RNA polymerase are recognized as a fundamental strategy for global reprogramming of gene expression to focus limited resources on synthesis of gene products essential to survival. In the late 1980s and early 1990s a wave of reports from several laboratories provided key observations that established RpoS/σS as a central regulator of starvation or stationary-phase gene expression in Escherichia coli. Among these was Mulvey and Loewen's sequencing of the katF gene (later renamed rpoS) that revealed homology to σ70 (1). Subsequent genetic studies by Lange and Hengge-Aronis identified katF as a gene that was induced in the late-exponential-to-stationary-phase transition and required for expression of several starvation/stationary-phase genes. This led to the proposal of the nomenclature of RpoS/σS for this putative alternate sigma subunit that controls a starvation/stationary-phase regulon (2).
Another important component of the story was reported in a classic Journal of Bacteriology paper in 1991 (3). McCann and colleagues demonstrated that KatF (RpoS) was required for cross protection from stresses, specifically, starvation-mediated resistance to osmotic, oxidative, and thermal stresses. This study was a logical progression of previous investigations from the Matin laboratory that had documented starvation-induced synthesis of specific proteins (4) and starvation-induced cross protection from oxidative (5) and osmotic (6) stresses. This body of research helped establish the global nature of the RpoS-mediated stress response, distinct from individual adaptive responses to challenges that confer resistance solely to the specific inducing stress. Through these and other studies, RpoS was established as the central player in the molecular mechanism through which E. coli adheres to the adage of Nietzsche “That which does not kill us makes us stronger.”
Although dwarfed by today's technologies for proteomics and expression profiling, the elegant two-dimensional electrophoretic analyses of pulse-labeled proteins employed by the Matin laboratory were instrumental in providing a key piece of the fundamental story of RpoS-mediated regulation of stress-protective genes that has become standard textbook knowledge. These studies laid the foundation for subsequent investigations that have uncovered the enormous complexity and exquisite fine-tuning of this seemingly simple strategy for gene regulation by an alternative sigma subunit. Genome-scale studies have indicated that RpoS activates ~10% of all E. coli genes, either directly or indirectly. The activity of this global regulator is highly regulated by transcriptional, translational, and proteolytic mechanisms, interfacing with several different signaling cascades as well as other transcription factors. The programming of gene expression to focus on maintenance and survival rather than a growth-oriented foraging/motile lifestyle is important in both free-living and host-associated environments. In addition to the early-recognized roles in protection from metabolic and environmental stresses, RpoS is involved in virulence, biofilm formation, cell shape, and stress-induced mutagenesis. Indeed, we now appreciate that there are few physiological activities of E. coli that are not influenced by RpoS.
The views expressed in this Editorial do not necessarily reflect the views of the journal or of ASM.