Evidence that Bacillus subtilis sporulation induced by the stringent response is caused by the decrease in GTP or GDP

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Abstract
Partial amino acid deprivation of B. subtilis, which evokes the stringent response, initiates sporulation not because the highly phosphorylated guanine nucleotides guanosine-5''-diphosphate-3''-diphosphate (ppGpp) and guanosine-5''-triphosphate-3''-diphosphate (pppGpp) increase but because GTP decreases. This was shown with a mutant (Myc) partially resistant to mycophenolate, an inhibitor of IMP dehydrogenase. Upon amino acid deprivation, the Myc mutant (62032) showed the usual increase in ppGpp and pppGpp but a reduced decrease in GTP and only a few cells sporulated. Extensive sporulation was restored by the addition of mycophenolate or decoyinine, an inhibitor of GMP synthetase, which caused a further decrease in GTP.