Susceptibility of Microsporum and Trichophyton species to suicide inhibitors of polyamine biosynthesis.
DFMO (difluoromethylornithine) and DFMA (difluoromethylarginine), irreversible suicide inhibitors of ornithine and arginine decarboxylase activities (ODC and ADC) respectively, inhibit the growth of six species of Microsporum and six species of Trichophyton. Trichophyton species in general, are more sensitive than Microsporum species. DFMA inhibits growth as effectively as DFMO but at a 10-fold lower concentration. Inhibition is specific, as a number of substrates and end products of ODC and ADC activities antagonize DFMA and DFMO (i.e. ornithine greater than putrescine = spermidine greater than agmatine). The methylester analogue of ornithine, MFMOme (monofluormethyldehydroornithine methylester) is at least a 25-fold more effective inhibitor than DFMO; the inhibition is specific as it is reversed by ornithine.
Boyle
S M
SM
Department of Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Sriranganathan
N
N
Cordes
D
D
D000935:Antifungal Agents; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003883:Arthrodermataceae / Q000187:drug effects; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors; D000518:Eflornithine / Q000031:analogs & derivatives / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008864:Microsporum / Q000187:drug effects*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000096:biosynthesis; D014249:Trichophyton / Q000187:drug effects*
D000935:Antifungal Agents; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; C030965:alpha-(difluoromethyl)arginine; D001120:Arginine; C047399:2-(fluoromethyl)dehydroornithine methyl ester; D002262:Carboxy-Lyases; C019722:arginine decarboxylase; D000518:Eflornithine