B , a homolog of stress-responsive B of Bacillus subtilis, controls both osmoprotection and differentiation in Streptomyces coelicolor A3 (2). Its gene is preceded by rsbA and rsbB genes encoding homologs of an anti-sigma factor, RsbW, and its antagonist, RsbV, of B. subtilis, respectively. Purified RsbA bound to B and prevented B -directed transcription from the sigBp1 promoter in vitro. An rsbA-null mutant exhibited contrasting behavior to the sigB mutant, with elevated sigBp1 transcription, no actinorhodin production, and precocious aerial mycelial formation, reflecting enhanced activity of B in vivo. Despite sequence similarity to RsbV, RsbB lacks the conserved phosphorylatable serine residue and its gene disruption produced no distinct phenotype. RsbV (SCO7325) from a putative six-gene operon (rsbV-rsbR-rsbS-rsbT-rsbU1-rsbU) was strongly induced by osmotic stress in a B -dependent manner. It antagonized the inhibitory action of RsbA on B -directed transcription and was phosphorylated by RsbA in vitro. These results support the hypothesis that the rapid induction of B target genes by osmotic stress results from modulation of B activity by the kinase-anti-sigma factor RsbA and its phosphorylatable antagonist RsbV, which function by a partnerswitching mechanism. Amplified induction could result from a rapid increase in the synthesis of both B and its inhibitor antagonist.Transcriptional regulators, especially sigma factors, play pivotal roles in the bacterial survival strategies such as stress responses, differentiation, social behavior, and pathogenesis (25,29). While the amounts of sigma factors are regulated through controlled synthesis and degradation, their activities are also regulated by other proteins, such as anti-sigma factors (28, 34). The activity of anti-sigma factors can be regulated by a network of other proteins, as best exemplified by the regulation of stress response and sporulation in Bacillus subtilis. There, the binding of anti-sigma factors RsbW and SpoIIAB to B and F , respectively, is regulated by their antagonist proteins, by a so called "partner-switching" mechanism, and involves interplay of various kinases and phosphatases (2,43,51).Streptomyces coelicolor is a gram-positive spore-forming soil bacterium that undergoes a complex cycle of morphological and physiological differentiation resembling that of filamentous fungi. The differentiation of S. coelicolor is dependent upon its ability to respond to changes in the environment, especially nutrient limitation, and is recognized as one of the processes to escape from the mitotic (vegetative) growth. Interplay of regulatory cascades with metabolic, morphological, homeostatic, and stress-related checkpoints has been proposed (15). Evidence for coupling differentiation with stress-related signals has accumulated in recent years. These include coregulation of stress stimulons with growth (developmental) transitions (45, 58) and participation of several stress-related sigma factors and/or their anti-sigma factors in initiating and completi...
