Regulation of bacteriophage lambda development by guanosine 5 '-diphosphate-3 '-diphosphate

On infection of its host, Escherichia coil, bacteriophage lambda can follow one of two alternative developmental pathways: lytic or lysogenic. Here we demonstrate that the "lysis-versus-lysogenization" decision is influenced by guanosine tetraphosphate (ppGpp), a nucleotide that is synthesized in E, coil cells in response to amino acid or carbon source starvation. We found that the efficiency of lysogenization is the highest at ppGpp concentratio ns somewhat higher than the basal level; too low and too high levels of ppG pp result in less efficient lysogenization. Maintenance of the already inte grated lambda prophage and phage lytic development were not significantly i nfluenced in the host lacking ppGpp. We found that the level of HflB/FtsH p rotease, responsible for degradation of the CII protein, an activator of "l ysogenic" promoters, depends on ppGpp concentration. The highest levels of HflB/FtsH was found in bacteria lacking ppGpp and in cells bearing increase d concentrations of this nucleotide. Using lacZ fusions, we investigated th e influence of ppGpp on activities of lambda promoters important at the sta ge of the lysis-versus-lysogenization decision. We found that each promoter is regulated differentially in response to the abundance of ppGpp. Moreove r, our results suggest that the cAMP level may influence ppGpp concentratio n in cells. The mechanism of the ppGpp-mediated control of lambda developme nt at the stage of the lysis-versus-lysogenization decision may be explaine d on the basis of differential influence of guanosine tetraphosphate on act ivities of p(L1) p(R), p(E), p(I), and p(aQ) promoters and by dependence of HflB/FtsH protease level on ppGpp concentration. (C) 1999 Academic Press.