An Alternative σ Factor, σ, Controls Avermectin Production and Multiple Stress Responses in

Alternative σ factors in bacteria redirect RNA polymerase to recognize alternative promoters, thereby facilitating coordinated gene expression necessary for adaptive responses. The gene () in encodes an alternative σ factor, σ, highly homologous to σ in . Studies reported here demonstrate that σ is an important regulator of both avermectin production and stress responses in . σ inhibited avermectin production by indirectly repressing expression of cluster-situated activator gene , and by directly initiating transcription of its downstream gene , which encodes a direct repressor of structural genes. σ had no effect on cell growth or morphological differentiation under normal growth conditions. Growth of a deletion mutant was less than that of wild-type strain on YMS plates following treatment with heat, HO, diamide, NaCl, or KCl. transcription was strongly induced by these environmental stresses, indicating response by σ itself. A series of σ-dependent genes responsive to heat, oxidative and osmotic stress were identified by EMSAs, qRT-PCR and transcription experiments. These findings indicate that σ plays an important role in mediating protective responses to various stress conditions by activating transcription of its target genes. Six σ-binding promoter sequences were determined and consensus binding sequence BGVNVH-N-GSNNHH (B: C, T or G, V: A, C or G, S: C or G, H: A, C or T, N: any nucleotide) was identified, leading to prediction of the σ regulon. The list consists of 940 putative σ target genes, assignable to 17 functional groups, suggesting the wide range of cellular functions controlled by σ in .