title: Mechanism of action of the antifungal antibiotic pyrrolnitrin.
abstract: Pyrrolnitrin at 10 mug/ml inhibited the growth of Saccharomyces cerevisiae, Penicillium atrovenetum, and P. oxalicum. The primary site of action of pyrrolnitrin on S. cerevisiae was the terminal electron transport system between succinate or reduced nicotinamide adenine dinucleotide (NADH) and coenzyme Q. At growth inhibitory concentrations, pyrrolnitrin inhibited endogenous and exogenous respiration immediately after its addition to the system. In mitochondrial preparations, the antibiotic inhibited succinate oxidase, NADH oxidase, succinate-cytochrome c reductase, NADH-cytochrome c reductase, and succinate-coenzyme Q(6) reductase. In addition, pyrrolnitrin inhibited the antimycin-insensitive reduction of dichlorophenolindophenol and of the tetrazolium dye 2,2'-di-p-nitrophenyl-(3,3'-dimethoxy-4,4'-bi-phenylene)5,5'-diphenylditetrazolium. The reduction of another tetrazolium dye, 2-p-iodophenyl-3-p-nitrophenyl-5-phenyltetrazolium chloride, that was antimycin-sensitive, was also inhibited by pyrrolnitrin. The antibiotic had no effect on the activity of cytochrome oxidase, and it did not appear to bind with flavine adenine dinucleotide, the coenzyme of succinic dehydrogenase. In whole cells of S. cerevisiae, pyrrolnitrin inhibited the incorporation of (14)C-glucose into nucleic acids and proteins. It also inhibited the incorporation of (14)C-uracil, (3)H-thymidine, and (14)C-amino acids into ribonucleic acid, deoxyribonucleic acid, and protein, respectively. The in vitro protein synthesis in Rhizoctonia solani and Escherichia coli was not affected by pyrrolnitrin. Pyrrolnitrin also inhibited the uptake of radioactive tracers, but there was no general damage to the cell membranes that would result in an increased leakage of cell metabolites. Apparently, pyrrolnitrin inhibits fungal growth by inhibiting the respiratory electron transport system.
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002247:Carbon Isotopes; D002474:Cell-Free System; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000096:biosynthesis; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D004926:Escherichia coli / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects; D009243:NAD / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D010407:Penicillium / Q000187:drug effects; D014176:Protein Biosynthesis; D011758:Pyrroles / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis; D012440:Saccharomyces / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D013386:Succinates / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D002247:Carbon Isotopes; D011758:Pyrroles; D013386:Succinates; D009243:NAD; D014451:Ubiquinone; D012313:RNA; D004247:DNA; D010088:Oxidoreductases; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV; D005947:Glucose