Multiple stress signal integration in the regulation of the complex σS-dependent csiD-ygaF-gabDTP operon in Escherichia coli

The csiD-ygaF-gabDTP region in the Escherichia coli genome represents a cluster of sigma(S)-controlled genes. Here, we investigated promoter structures, sigma factor dependencies, potential co-regulation and environmental regulatory patterns for all of these genes. We find that this region constitutes a complex operon with expression being controlled by three differentially regulated promoters: (i) csiD(p), which affects the expression of all five genes, is cAMP-CRP/sigma(S)-dependent and activated exclusively upon carbon starvation and stationary phase; (ii) gabD(p1), which is sigma(S)-dependent and exhibits multiple stress induction like sigma(S) itself; and (iii) gabD(p2)[previously suggested by Schneider, B.L., Ruback, S., Kiupakis, A.K., Kasbarian, H., Pybus, C., and Reitzer, L. (2002) J. Bacteriol. 184: 6976-6986], which appears to be Nac/sigma(70)-controlled and to respond to poor nitrogen sources. In addition, we identify a novel repressor, CsiR, which modulates csiD(p) activity in a temporal manner during early stationary phase. Finally, we propose a physiological role for sigma(S)-controlled GabT/D-mediated gamma-aminobutyrate (GABA) catabolism and glutamate accumulation in general stress adaptation. This physiological role is reflected by the activation of the operon-internal gabD(p1) promoter under the different conditions that also induce sigma(S), which include shifts to acidic pH or high osmolarity as well as starvation or stationary phase.