Mode of Action and Resistance to Azole Antifungals Associated with the Formation of 14α-Methylergosta-8,24(28)-dien-3β,6α-diol
Azole antifungal compounds inhibit sterol 14α-demethylase. They are used extensively for the treatment of immunocompromised patients where fungal infection is common and often results in death. Resistance to the compounds is emerging, particularly in fungal pathogens obtained from AIDS patients unde...
Saved in:
Published in | Biochemical and biophysical research communications Vol. 207; no. 3; pp. 910 - 915 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
1995
|
Online Access | Get full text |
Cover
Loading…
Summary: | Azole antifungal compounds inhibit sterol 14α-demethylase. They are used extensively for the treatment of immunocompromised patients where fungal infection is common and often results in death. Resistance to the compounds is emerging, particularly in fungal pathogens obtained from AIDS patients undergoing prolonged therapy. We show here that cell growth arrest correlates with the accumulation of 14α-methyl-ergosta-8,24(28)-dien-3β,6α-diol in a yeast strain with a sterol 14α-demethylase gene disruption, which mimics stringent treatment conditions. Cells can overcome the effect of such a block by a suppressor mutation in sterol Δ
5,6 desaturation and acquire azole resistance. Plasmid-based complementation of the sterol 14α-demethylase defect does not alter the azole susceptibility of strains containing these suppressor mutations, showing resistance is due entirely to the Δ
5,6 desaturase defect. |
---|---|
ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1006/bbrc.1995.1272 |