title: Induction of a stable sigma factor SigR by translation-inhibiting antibiotics confers resistance to antibiotics.
abstract: Antibiotic-producing streptomycetes are rich sources of resistance mechanisms against endogenous and exogenous antibiotics. An ECF sigma factor σ(R) (SigR) is known to govern the thiol-oxidative stress response in Streptomyces coelicolor. Amplification of this response is achieved by producing an unstable isoform of σ(R) called σ(R'). In this work, we present evidence that antibiotics induce the SigR regulon via a redox-independent pathway, leading to antibiotic resistance. The translation-inhibiting antibiotics enhanced the synthesis of stable σ(R), eliciting a prolonged response. WblC/WhiB7, a WhiB-like DNA-binding protein, is responsible for inducing sigRp1 transcripts encoding the stable σ(R). The amount of WblC protein and its binding to the sigRp1 promoter in vivo increased upon antibiotic treatment. A similar phenomenon appears to exist in Mycobacterium tuberculosis as well. These findings reveal a novel antibiotic-induced resistance mechanism conserved among actinomycetes, and also give an explicit example of overlap in cellular damage and defense mechanisms between thiol-oxidative and anti- translational stresses.
authors.affiliation: Laboratory of Molecular Microbiology, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul 151-742, Korea.
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: Laboratory of Molecular Microbiology, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul 151-742, Korea.
authors.forename: Gyeong-Seok
authors.initials: GS
authors.lastname: Oh
authors.affiliation: Korean Institute of Tuberculosis, 168-5, Osongsaengmyeong 4-ro, Osong, Cheongwon-gun, Chungcheongbuk-do, 28158, Korea.
authors.forename: Sungweon
authors.initials: S
authors.lastname: Ryoo
authors.affiliation: Laboratory of Molecular Microbiology, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul 151-742, Korea.
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Roe
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D005167:Factor VII / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D018085:Regulon / Q000235:genetics; D012808:Sigma Factor / Q000235:genetics*; D048372:Streptomyces coelicolor / Q000187:drug effects / Q000235:genetics; D013438:Sulfhydryl Compounds / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D012808:Sigma Factor; D013438:Sulfhydryl Compounds; D005167:Factor VII