Mycothiol regulates and is regulated by a thiol-specific antisigma factor RsrA and sigma(R) in Streptomyces coelicolor.
Mycothiol (MSH) is a small thiol molecule with a cysteine-ligated disaccharide structure found in actinomycetes that include streptomycetes and mycobacteria. In Streptomyces coelicolor, a model organism for antibiotic production and differentiation, the amount of MSH is under the control of a sigma factor sigma(R), which is regulated by an antisigma factor RsrA with a thiol-disulphide redox switch. We found that the first gene (mshA) in the biosynthetic pathway for MSH and the gene for amidase (mca) that participates in detoxifying mycothiol-reactive drugs are under direct control of sigma(R). The sigma(R) target genes are induced not only by a thiol oxidant diamide, but also by alkylating agents that cause a rapid decrease in MSH. Expression of the sigma(R) regulon was also elevated in MSH-deficient mutants, suggesting that a decrease in the level of MSH is a natural intracellular trigger for sigma(R) activation. We found that MSH was capable of reducing RsrA to bind sigma(R), whereas glutathione was not. These results support a proposal that the RsrA-sigma(R) system senses the intracellular level of reduced MSH, and that MSH serves as a natural modulator of the transcription system for its own replenishment in addition to being a redox buffer and drug detoxifier.
Park
Joo-Hong
JH
School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 151-742, Korea.
Roe
Jung-Hye
JH
D000477:Alkylating Agents / Q000494:pharmacology; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism*; D003545:Cysteine / Q000235:genetics* / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006020:Glycopeptides / Q000235:genetics* / Q000378:metabolism*; D007294:Inositol / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D018085:Regulon; D012808:Sigma Factor / Q000378:metabolism*; D048372:Streptomyces coelicolor / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D000477:Alkylating Agents; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006020:Glycopeptides; C121147:RsrA protein, Streptomyces coelicolor; D012808:Sigma Factor; D014157:Transcription Factors; C089265:mycothiol; D007294:Inositol; D000581:Amidohydrolases; C019665:amidase; D003545:Cysteine