THE GUANOSINE NUCLEOTIDE (P)PPGPP INITIATES DEVELOPMENT AND A-FACTOR PRODUCTION IN MYXOCOCCUS-XANTHUS

Guanosine 3'-di-5'-(tri)di-phosphate nucleotides [(p)ppGpp], synthesiz ed in response to amino acid limitation, induce early gene expression leading to multicellular fruiting body formation in Myxococcus xanthus . A mutant (DK527) that fails to accumulate (p)ppGpp in response to st arvation was found to be blocked in development prior to aggregation. By use of a series of developmentally regulated Tn5lac transcriptional fusion reporters, the time of developmental arrest in DK527 was narro wed to within the few hours of development, the period of starvation r ecognition. The mutant is also defective in the production of A-factor , an early extracellular cell-density signal. The relA gene from Esche richia coli, which encodes a ribosome-dependent (p)ppGpp synthetase, r escues this mutant. We also demonstrate that inactivation of the M. xa nthus relA homolog blocks development and the accumulation of (p)ppGpp . Moreover, the wild-type allele of Myxococcus relA rescues DK527. The se observations support a model in which accumulation of (p)PPGPP, in response to starvation, initiates the program of fruiting body develop ment, including the production of A-factor.