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Drug Target Elucidation Through Isolation and Analysis of Drug-Resistant Mutants in Cryptococcus Neoformans

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Specialty Molecular Biology
Date 2023 Apr 6
PMID 37024699
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Abstract

Drug target identification is an essential component to antifungal drug development. Many methods, including large chemical library screening, natural product screening, and drug repurposing efforts, can identify compounds with favorable in vitro antifungal activity. However, these approaches will often identify compounds with no known mechanism of action. Herein, we describe a method utilizing the human fungal pathogen Cryptococcus neoformans to identify antifungal drug targets through the isolation of spontaneous resistant mutants, antifungal testing, whole-genome sequencing, and variant analysis.

References
1.
Odom A, Muir S, Lim E, Toffaletti D, Perfect J, Heitman J . Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J. 1997; 16(10):2576-89. PMC: 1169869. DOI: 10.1093/emboj/16.10.2576. View

2.
Roemer T, Xu D, Singh S, Parish C, Harris G, Wang H . Confronting the challenges of natural product-based antifungal discovery. Chem Biol. 2011; 18(2):148-64. DOI: 10.1016/j.chembiol.2011.01.009. View

3.
Friedman R, Gish S, Brown H, Brier L, Howard N, Doering T . Unintended Side Effects of Transformation Are Very Rare in . G3 (Bethesda). 2018; 8(3):815-822. PMC: 5844303. DOI: 10.1534/g3.117.300357. View

4.
Huang D, LeBlanc E, Shekhar-Guturja T, Robbins N, Krysan D, Pizarro J . Design and Synthesis of Fungal-Selective Resorcylate Aminopyrazole Hsp90 Inhibitors. J Med Chem. 2019; 63(5):2139-2180. PMC: 7069776. DOI: 10.1021/acs.jmedchem.9b00826. View

5.
Perlatti B, Harris G, Nichols C, Ekanayake D, Alspaugh J, Gloer J . Campafungins: Inhibitors of and Hyphal Growth. J Nat Prod. 2020; 83(9):2718-2726. PMC: 7530089. DOI: 10.1021/acs.jnatprod.0c00641. View