Mechanism of action of rifampin on Mycobacterium smegmatis.
Deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase (EC 2.7.7.6) isolated from a rifampin-sensitive strain of Mycobacterium smegmatis was 90% inhibited by 1 mug of rifampin per ml; enzyme from a rifampin-resistant mutant was not affected by this concentration of antibiotic. Inhibition of phenylalanine-1-(14)C incorporation by rifampin in growing cultures was complete about 6 min after addition of antibiotic. Under the same conditions, uracil-2-(14)c incorporated was blocked after 1.5 to 2 min. Rifampin kills M. smegmatis very slowly. When rifampin-inhibited cultures were transferred to a rifampin-free medium, there was a partial resumption of uracil-2-(14)C incorporation, even in the presence of chloramphenicol. We conclude that a primary event in the inhibition of M. smegmatis by rifampin is the block of DNA-dependent RNA polymerase.
D000249:Adenosine Monophosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis; D001431:Bacteriological Techniques; D002247:Carbon Isotopes; D002474:Cell-Free System; D003470:Culture Media; D004352:Drug Resistance, Microbial; D005827:Genetics, Microbial; D009161:Mycobacterium / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D012316:RNA Nucleotidyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012329:RNA, Bacterial / Q000096:biosynthesis; D012293:Rifampin / Q000494:pharmacology*; D013997:Time Factors; D014498:Uracil / Q000378:metabolism
D001426:Bacterial Proteins; D002247:Carbon Isotopes; D003470:Culture Media; D012329:RNA, Bacterial; D000249:Adenosine Monophosphate; D010649:Phenylalanine; D014498:Uracil; D012316:RNA Nucleotidyltransferases; D012293:Rifampin