Respiratory chain of a pathogenic fungus, Microsporum gypseum: effect of the antifungal agent pyrrolnitrin.
Pyrrolnitrin has been reported to inhibit Bacillus megaterium primarily by forming complexes with phospholipids and to block electron transfer of Saccharomyces cerevisiae between succinate or reduced nicotinamide adenine dinucleotide (NADH) and coenzyme Q. We found that pyrrolnitrin inhibited respiration of conidia of Microsporum gypseum. In mitochondrial preparations, pyrrolnitrin strongly inhibited respiration and the rotenone-sensitive NADH-cytochrome c reductase. The rotenone-insensitive NADH-cytochrome c reductase, the succinate-cytochrome c reductase, and the reduction of dichlorophenolindophenol by either NADH or succinate were inhibited to a lesser extent. However, the activity of cytochrome oxidase was not affected by pyrrolnitrin. The extent of reduction of flavoproteins by NADH and succinate, measured at 465 - 510 nm, was unaltered; however, the reduction of cytochrome b, measured at 560 - 575 nm, was partially inhibited by pyrrolnitrin. The level of totally reduced cytochrome b was restored with antimycin A. We, therefore, concluded that the primary site of action of this antifungal antibiotic is to block electron transfer between the flavoprotein of the NADH-dehydrogenase and cytochrome b segment of the respiratory chain of M. gypseum.
D000814:Aniline Compounds; D000935:Antifungal Agents / Q000494:pharmacology*; D000968:Antimycin A / Q000494:pharmacology; D001205:Ascorbic Acid; D003470:Culture Media; D003580:Cytochromes / Q000378:metabolism; D004566:Electrodes; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D005415:Flavins / Q000378:metabolism; D008864:Microsporum / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009243:NAD; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D011048:Polarography; D011758:Pyrroles / Q000494:pharmacology*; D012402:Rotenone / Q000494:pharmacology; D013053:Spectrophotometry; D013386:Succinates
D000814:Aniline Compounds; D000935:Antifungal Agents; D003470:Culture Media; D003580:Cytochromes; D005415:Flavins; D011758:Pyrroles; D013386:Succinates; D012402:Rotenone; D009243:NAD; D000968:Antimycin A; D010088:Oxidoreductases; D003576:Electron Transport Complex IV; D001205:Ascorbic Acid