AUTHOR=Sun Xianyun , Wang Wenzhao , Wang Kangji , Yu Xinxu , Liu Jie , Zhou Fucai , Xie Baogui , Li Shaojie 

TITLE=Sterol C-22 Desaturase ERG5 Mediates the Sensitivity to Antifungal Azoles in Neurospora crassa and Fusarium verticillioides

JOURNAL=Frontiers in Microbiology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2013.00127

DOI=10.3389/fmicb.2013.00127

ISSN=1664-302X

ABSTRACT=<p>Antifungal azoles inhibit ergosterol biosynthesis by interfering with lanosterol 14α-demethylase. In this study, seven upregulated and four downregulated ergosterol biosynthesis genes in response to ketoconazole treatment were identified in <italic>Neurospora crassa</italic>. Azole sensitivity test of knockout mutants for six ketoconazole-upregulated genes in ergosterol biosynthesis revealed that deletion of only sterol C-22 desaturase ERG5 altered sensitivity to azoles: the <italic>erg5</italic> mutant was hypersensitive to azoles but had no obvious defects in growth and development. The <italic>erg5</italic> mutant accumulated higher levels of ergosta 5,7-dienol relative to the wild type but its levels of 14α-methylated sterols were similar to the wild type. ERG5 homologs are highly conserved in fungal kingdom. Deletion of <italic>Fusarium verticillioides</italic><italic>erg5</italic> also increased ketoconazole sensitivity, suggesting that the roles of ERG5 homologs in azole resistance are highly conserved among different fungal species, and inhibition of ERG5 could reduce the usage of azoles and thus provide a new target for drug design.</p>