Chemogenomic profiling in yeast reveals antifungal mode-of-action of polyene macrolactam auroramycin

• DOI: 10.1371/journal.pone.0218189
• Publication Date: 2019-06-10T17:36:46Z
• Authors: Jin Huei Wong; Mohammad Alfatah; Kiat Whye Kong; Shawn Hoon; Wan Lin Yeo; Kuan Chieh Ching; Corinna Jie Hui Goh; Mingzi M. Zhang; Yee Hwee Lim; Fong Tian Wong; Prakash Arumugam
• Keywords: Mode of Action; Polyene; Aspergillus nidulans

In this study, we report antifungal activity of auroramycin against Candida albicans, tropicalis, and Cryptococcus neoformans. Auroramycin, a potent antimicrobial doubly glycosylated 24-membered polyene macrolactam, was previously isolated characterized, following CRISPR-Cas9 mediated activation silent polyketide synthase biosynthetic gene cluster in Streptomyces rosesporous NRRL 15998. Chemogenomic profiling yeast has linked its bioactivity to vacuolar transport membrane organization. This verified by disruption structure integrity cells with treatment. Addition salt but not sorbitol the medium rescued growth auroramycin-treated suggesting that causes ionic stress. Furthermore, caused hyperpolarization plasma displayed synergistic interaction cationic hygromycin. Our data strongly suggest inhibits causing leakage cations from cytoplasm. Thus, auroramycin's mode-of-action is distinct known polyenes, reinforcing importance natural products discovery new anti-infectives.