Ectopic production of guanosine penta- and tetraphosphate can initiate early developmental gene expression in Myxococcus xanthus.

Amino acid or carbon limitation is sufficient to initiate fruiting body development in Myxococcus xanthus. In both Escherichia coli and M. xanthus the levels of guanosine 3'-di-5'-(tri)di-phosphate nucleotides [(p)ppGpp] rise transiently when cells are starved for amino acids or carbon. Ectopic increase in the intracellular concentration of (p)ppGpp was achieved in M. xanthus by introducing a copy of the E. coli relA gene, whose product catalyzes pyrophosphate transfer from ATP- to GTP-forming pppGpp. The E. coli RelA protein was detected in these M. xanthus strains, and a rise in (p)ppGpp was observed chromatographically. This increase in the intracellular (p)ppGpp levels was sufficient to activate developmentally specific gene expression. Although (p)ppGpp is made from GTP, the intracellular GTP pool from these strains was not significantly decreased. Moreover, when the GTP pool was lowered by either of two specific inhibitors of GTP synthesis, mycophenolic acid or decoyinine, development was not induced. These results suggest that M. xanthus cells can assess their nutritional status by monitoring the internal availability of amino acids through (p)ppGpp levels.