Role of Sterol Derivatives Depletion Under Azole Stress in Fungi

Abstract

Azole antifungals target the sterol biosynthesis in fungal cell membrane and disrupt sterol biosynthesis pathway. In response to antifungal azoles fungal cell upregulate the transcriptions of drug efflux pumps in the membrane or the sterol regulatory gene in the fungal cell membrane. These transcriptional upregulationsare generated due to accumulation or the reductions of the sterol derivatives in azole stress. Study demonstrated the azole target ERG 11 similar protein mutant response in Neurosporacrassa under azole stress. Which revealed the transcriptional upregulation of all three cytochrome P450 homolog genes mutants in ketoconazole stress as compare to the controls using qRT-PCR. That were further justified by HPLC-MS. That suggested that ketoconazole responsive gene transcriptions pattern were similar in cyp450 homolog genes mutants for ERG11, ERG6, ERG25, ERG5 and ERG 3 gene in sterol biosynthesis. Whereas the accumulations of the sterol derivatives lanosterol, eburicol was increased in the CYP 450 mutants after ketoconazole stress. On the other hand the toxic derivative fecosterol and the ergosterol contents were reduced after ketoconazole stress and didnot altered the fungal morphology. Study indicated that in azole stress ERG11 similar protein mutants deplete sterol derivatives and do not induce antifungal drug resistance in Neurosporacrassa.