The actinobacteria-specific gene wblA controls major developmental transitions in Streptomyces coelicolor A3(2)

Abstract

The Streptomyces coelicolor A3(2) sporulation gene whiB is the paradigm of a family of genes (wbl, whiB-like) that are confined to actinobacteria. The chromosome of S. coelicolor contains 11 wbl genes, among which five are conserved in many actinobacteria: whiB itself; whiD, a sporulation gene; wblC, which is required for multi-drug resistance; and wblA and wblE, whose roles had previously been little studied. We succeeded in disrupting wblA and the six non-conserved genes, but could not disrupt wblE. Although mutations in the six non-conserved wbl genes (including some multiple wbl mutants) produced no readily detectable phenotype, mutations in wblA had novel and complex effects. The aerial mycelium of wblA mutants was coloured red, because of the ectopic presence of pigmented antibiotics (actinorhodin and undecylprodigiosin) normally confined to lower parts of wild-type colonies, and consisted almost entirely of non-sporulating, thin, straight filaments, often bundled together in a fibrillar matrix. Rare spore chains were also formed, which exhibited wild-type properties but were genetically still wblA mutants. A wblA mutant achieved higher biomass than the wild-type. Microarray analysis indicated major transcriptional changes in a wblA mutant: using a relatively stringent cut-off, 183 genes were overexpressed, including genes for assimilative primary metabolism and actinorhodin biosynthesis, and 103 were underexpressed, including genes associated with stages of aerial hyphal growth. We suggest that WblA is important in both the slow-down of biomass accumulation and the change from aerial hyphal initial cells to the subapical stem and apical compartments that precede sporulation; and that the mutant aerial mycelium consists of recapitulated defective aerial hyphal initial cells.

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

“…On the other hand, a high copy number of wblA depressed the production of ACT, RED, and CDA in S. coelicolor (and of doxorubicin in S. peucetius) (200). It was suggested that WblA mediates a switch between antibiotic production and morphological development, such that (as suggested above for WhiJ systems) mutation of wblA causes increased representation in the colony of an antibiotic-producing cell type that is intermediate between growth and a developmentally committed state (195).…”

“…These small, redox-and nitric oxide-sensitive iron-sulfur proteins are widespread in actinobacteria and are absent from all other bacteria (195). Disruption of wblA dramatically increased antibiotic production in S. coelicolor (195), Streptomyces peucetius (196), and Streptomyces sp.…”

“…These small, redox-and nitric oxide-sensitive iron-sulfur proteins are widespread in actinobacteria and are absent from all other bacteria (195). Disruption of wblA dramatically increased antibiotic production in S. coelicolor (195), Streptomyces peucetius (196), and Streptomyces sp. strain C4412 (197), prevented nearly all aerial hyphae from sporulating in S. coelicolor (195) and Streptomyces ghanaensis (198), affected the expression of hundreds of genes in S. coelicolor (195), and slightly increased S. coelicolor oxidative stress responses (199).…”

“…Disruption of wblA dramatically increased antibiotic production in S. coelicolor (195), Streptomyces peucetius (196), and Streptomyces sp. strain C4412 (197), prevented nearly all aerial hyphae from sporulating in S. coelicolor (195) and Streptomyces ghanaensis (198), affected the expression of hundreds of genes in S. coelicolor (195), and slightly increased S. coelicolor oxidative stress responses (199). On the other hand, a high copy number of wblA depressed the production of ACT, RED, and CDA in S. coelicolor (and of doxorubicin in S. peucetius) (200).…”

“…Another developmental gene, wblA, encodes one of 11 S. coelicolor proteins of the Wbl (WhiB-like) family (195). These small, redox-and nitric oxide-sensitive iron-sulfur proteins are widespread in actinobacteria and are absent from all other bacteria (195).…”