title: Genome-wide transcriptome analysis reveals that a pleiotropic antibiotic regulator, AfsS, modulates nutritional stress response in Streptomyces coelicolor A3(2).
abstract: BACKGROUND
  A small "sigma-like" protein, AfsS, pleiotropically regulates antibiotic biosynthesis in Streptomyces coelicolor. Overexpression of afsS in S. coelicolor and certain related species causes antibiotic stimulatory effects in the host organism. Although recent studies have uncovered some of the upstream events activating this gene, the mechanisms through which this signal is relayed downstream leading to the eventual induction of antibiotic pathways remain unclear.
  
  
  RESULTS
  In this study, we employed whole-genome DNA microarrays and quantitative PCRs to examine the transcriptome of an afsS disruption mutant that is completely deficient in the production of actinorhodin, a major S. coelicolor antibiotic. The production of undecylprodigiosin, another prominent antibiotic, was, however, perturbed only marginally in the mutant. Principal component analysis of temporal gene expression profiles identified two major gene classes each exhibiting a distinct coordinate differential expression pattern. Surprisingly, nearly 70% of the >117 differentially expressed genes were conspicuously associated with nutrient starvation response, particularly those of phosphate, nitrogen and sulfate. Furthermore, expression profiles of some transcriptional regulators including at least two sigma factors were perturbed in the mutant. In almost every case, the effect of afsS disruption was not observed until the onset of stationary phase.
  
  
  CONCLUSIONS
  Our data suggests a comprehensive role for S. coelicolor AfsS as a master regulator of both antibiotic synthesis and nutritional stress response, reminiscent of alternative sigma factors found in several bacteria.
authors.affiliation: Department of Chemical Engineering and Materials Science, University of Minnesota, 421 Washington Ave. SE., Minneapolis, MN 55455, USA. wei.lian@abbott.com
authors.forename: Wei
authors.initials: W
authors.lastname: Lian
authors.forename: Karthik P
authors.initials: KP
authors.lastname: Jayapal
authors.forename: Salim
authors.initials: S
authors.lastname: Charaniya
authors.forename: Sarika
authors.initials: S
authors.lastname: Mehra
authors.forename: Frank
authors.initials: F
authors.lastname: Glod
authors.forename: Yun-Seung
authors.initials: YS
authors.lastname: Kyung
authors.forename: David H
authors.initials: DH
authors.lastname: Sherman
authors.forename: Wei-Shou
authors.initials: WS
authors.lastname: Hu
mesh_terms: D000880:Anthraquinones / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D002876:Chromosomes, Bacterial; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D016680:Genome, Bacterial / Q000235:genetics; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D009154:Mutation; D009584:Nitrogen / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010710:Phosphates / Q000172:deficiency; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012808:Sigma Factor / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D048372:Streptomyces coelicolor / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D013884:Thiosulfate Sulfurtransferase / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D000095622:Benzoisochromanequinones
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005974:Glutamate-Ammonia Ligase; D009584:Nitrogen; D010710:Phosphates; D012808:Sigma Factor; D013431:Sulfates; D013884:Thiosulfate Sulfurtransferase; C013390:actinorhodin; D000095622:Benzoisochromanequinones