Author(s):
1. Fatima Ismail:
Department of Biochemistry IBBB, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
Abstract:
The azoles are the most widely used antifungal drugs. Their target ERG-11 and its downstream protein ERG-5 play significant roles in resistance to the azoles. Both of them belong to the cytochrome P450 family proteins. There are many other P450 family proteins, but their contribution to fungal drug-resistance mechanism is not clear. 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 upregulations are generated due to accumulation or the reductions of the sterol derivatives in azole stress. Study demonstrated the azole target ERG 11 paralog mutant response in Neurospora crassa 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 and 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 altered the fungal morphology. Study indicated that in azole stress ERG11 similar protein mutants deplete sterol derivatives and suppress the antifungal drug resistance in Neurospora crassa.
Page(s):
60-60
DOI:
DOI not available
Published:
Journal: Abstract Book on Global Science Technology and Management Conference, Volume: 0, Issue: 0, Year: 2023
Keywords:
Antifungal Drug Resistance
,
Pathogenic fungi
,
Molecular Mechanism
References:
References are not available for this document.
Citations
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