Abstract
BackgroundA 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.ResultsIn 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.ConclusionOur 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.
Highlights
A small "sigma-like" protein, AfsS, pleiotropically regulates antibiotic biosynthesis in Streptomyces coelicolor
The most significant change was observed for the polyketide antibiotic, actinorhodin, which normally accumulates to significant levels in M145 giving the culture a distinctive deep blue color
This finding is much more dramatic than earlier reports where synthesis of actinorhodin was observed in afsS deletion strains [19], albeit to a much lesser extent compared to wild-type
Summary
A small "sigma-like" protein, AfsS, pleiotropically regulates antibiotic biosynthesis in Streptomyces coelicolor. It is wellknown that antibiotic biosynthesis in bacteria is generally elicited as a physiological response to a variety of environmental stimuli including high cell density, nutritional imbalance and/or presence of stress-inducing agents. Evidence hinting at the interplay between stress signals and antibiotic synthesis have emerged with the findings that mutants of several Streptomyces coelicolor sigma factors implicated in stress-response are perturbed in antibiotics production [2,3,4,5,6,7,8]. Despite extensive efforts aimed at elucidating antibiotic regulatory pathways, the exact chain of molecular events leading from sensing of stress or nutritional starvation signal to the eventual activation of antibiotic pathways remains largely obscure
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