Effects of triazoles on fungi: V. Response by a naturally tolerant species,Mucor rouxii

The responses ofMucor rouxii to propiconazole, and in some cases etaconazole, with respect to lipid metabolism were compared with those ofAspergillus ochraceus andRhizopus stolonifer which exhibit higehr sensitivity to this triazole by factors of 50 and 10, respectively. Propiconazole inhibited the C-14 demethylation of lanosterol in each of the species tested, which resulted in a dose-related decrease in ergosterol and increase in C-14 methyl sterols. The principal C-14 methyl sterol that accumulated with inhibitor treatment was 24-methylene dihydrolanosterol. The tolerance ofM. rouxii could not be explained by reduced inhibitor uptake, alteration of the inhibitor binding site, or detoxification through metabolism since C-14 methyl sterols accumulated in mycelium treated with 2.0 μg/ml propiconazole, a concentration 40 times less than that required for 50% growth inhibition and at which no growth inhibition was detected in this species, and one that gave over 50% inhibition ofA. ochraceus. Other alterations in lipid metabolism that accompany treatment with sterol inhibitors in relatively sensitive species, i.e., accumulation of free fatty acids and increase in linoleic acid (C_18:2), were not observed inM. rouxii orR. stolonifer, but they were found inA. ochraceus. The results of this study suggest that the quantitative and perhaps the qualitative nature of the requirement for sterols may be different inM. rouxii, and perhaps other tolerant Mucorales, than in the more sensitive fungi.