ATP synthesis inhibitor at subinhibitory concentration

Knockout of respiratory enzymes causes developmental defects in Streptomyces coelicolor A3(2). The mutant cells upregulated the transcription of certain housekeeping genes including the ATP synthase operon. This was likely to be a homeostatic response to respiratory impairment. The respiratory mutants contained a high level of intracellular ATP, and performed effective cellular differentiation and antibiotic production if ATP synthesis inhibitors were exogenously supplied. Based on this observation, we hypothesize that the intracellular ATP level is critical for Streptomyces development. The stimulatory effect of ATP synthesis inhibitors turns out to be an instance of the divergent actions of antibiotic compounds exerted at a subinhibitory concentration. The evidence provides an explanation regarding the physiological background fundamental to such an effect of antibiotics.