Quinone induced stringent control. Accumulation of ppGpp and inhibition of RNA synthesis in stringent Escherichia coli by 5,8-dioxo-6-amino-7-chloroquinoline.
The mode of action of a synthetic cytostatic quinone was studied in Escherichia coli. 1. At concentrations of 1.5-6 mug/ml, 5,8-dioxo-6-amino-7-chloroquinoline rapidly inhibits growth and protein synthesis in E. coli. The synthesis of RNA is immediately affected in E. coli rel+ whereas in E. coli rel- the accumulation of RNA can proceed on addition of the quinone. This indicates that the inhibition of RNA synthesis in the stringent strain is a consequence of the regulatory phenomenon governed by the rel gene. 2. Chloramphenicol, known to abolish the stringent control mechanism, added simultaneously with the quinone allows the accumulation of RNA to proceed in the stringent strain. 3. Guanosine tetraphosphate accumulates in quinone-treated E. coli rel+ but not in the relaxed mutant strain. 4. Addition of amino acids reverses all inhibitory effects observed in quinone treated stringent and relaxed cells. 5. It is concluded that the bacteriostatic effect of 5,8-dioxo-6-amino-7-chloroquinoline on E. coli is caused by an apparent intracellular amino acid starvation.
D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis*; D002250:Carbon Radioisotopes; D002701:Chloramphenicol / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000096:biosynthesis*; D007659:Ketones / Q000494:pharmacology; D010649:Phenylalanine / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D012329:RNA, Bacterial / Q000096:biosynthesis*; D014316:Tritium; D014529:Uridine / Q000378:metabolism
D000596:Amino Acids; D000634:Aminoquinolines; D001426:Bacterial Proteins; D002250:Carbon Radioisotopes; D006150:Guanine Nucleotides; D007659:Ketones; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D012329:RNA, Bacterial; D014316:Tritium; C018817:6-amino-7-chloro-5,8-dioxoquinoline; D010649:Phenylalanine; D002701:Chloramphenicol; D000409:Alanine; D014529:Uridine