Regulation of Macromolecular Synthesis by Putrescine in a Conditional Escherichia coli Putrescine Auxotroph

Abstract

Addition of putrescine to a slowly growing, polyamine-starved Escherichia coli K-12 mutant conditionally incapable of synthesizing putrescine causes the immediate stimulation of protein synthesis. After a period ranging from 60 to 105 min, ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) syntheses are also stimulated and rapid cellular division begins. Chloramphenicol blocks this rapid cellular division, although addition of the specific DNA synthesis inhibitor, nalidixic acid, has no effect on cell division. By sucrose gradient analysis and diethylaminoethyl-cellulose chromatography, the proteins initially made in response to putrescine appear to be composed of many classes, including membrane-bound proteins. However, the synthesis of ribosomal subunits is not altered during this period. A possible role for putrescine in either the stimulation of messenger RNA transcription or in translation is suggested.

Role of Polyamines in the Control of Cell Proliferation and Differentiation

“…The adverse effects exerted by these polyamine synthesis inhibitors on macromolecular synthesis were potentiated when the drugs were used in combination, yet their action appeared to be specific, because the rate of synthesis of nucleic acids and protein could be completely reversed by low concentrations of exogenous polyamines. The importance of the polyamines for protein synthesis is strongly supported by the finding that addition of putrescine to a slowly growing, polyamine-depleted mutant of E. coli K12, conditionally incapable of synthesizing putrescine, caused the immediate stimulation of protein synthesis [148]. After a lag period, RNA and DNA synthesis were also stimulated and rapid cellular division began.…”

Control of cell division in bacteria.

“…However, some tentative generalizations concerning conditions which favor either filament formation or division can be made. Generally, filament formation is: (i) caused by a low dose of an agent which inhibits growth; (ii) enhanced by fast growth in rich media (e.g., 2,40,59,144,149,152); (iii) reversed by suddenly slowing growth (chloramphenicol treatment; 17, 43, 152), nutritional shift down (144), or "liquid holding" (73,74). In fact, it seems possible that any chemical at some concentration, whether attainable in the laboratory or not, could cause filament formation.…”

Cadaverine in Bacteriophage T4

“…Dion and Cohen's experiments with a polyamine auxotroph (7,8) demonstrated that (i) cellular DNA synthesis was greatly stimulated by the addition of putrescine or spermidine but not by cadaverine, and that (ii) phage DNA synthesis was dependent on polyamine synthesis or addition. More recent experiments indicated that the primary effect of putrescine addition to putrescine-depleted cells is to stimulate protein synthesis insofar as an increased rate of leucine incorporation preceded an increase in the rates of uracil or thymine incorporation (30). Dion and Cohen (7,8) found no putrescine or spermidine in the auxotroph, but the starved cells which could replicate slowly contained small amounts of cadaverine and a new spermidine homologue that is apparently derived from cadaverine.…”