Armstrong Joseph O, Jiang Pengyao, Tsai Skyler, Phan Megan My-Ngan, Harris Kelley, Dunham Maitreya J
Department of Genome Sciences, University of Washington.
Center for Mechanisms of Evolution, Biodesign Institute, School of Life Sciences, Arizona State University.
bioRxiv. 2024 Jun 5:2024.06.03.597250. doi: 10.1101/2024.06.03.597250.
is frequently used in the yeast community as the mutation target for 5-fluoroorotic acid (5-FOA) resistance. We identified a novel class of mutants that can grow in the presence of 5-FOA. Unlike mutants, mutants remain prototrophic and grow in the absence of uracil. In addition to 5-FOA resistance, we found that mutations to also confer resistance to 5-fluorocytosine (5-FC) and 5-fluorouracil (5-FU). In total, we identified 50 unique missense mutations across 32 residues of . We found that 28 out of the 32 affected residues are located in regions conserved between and three clinically relevant pathogenic fungi. These findings suggest that mutations to present a second target for mutation screens utilizing 5-FOA as a selection marker as well as a potential mode of resistance to the antifungal therapeutic 5-FC.
在酵母群体中经常被用作5-氟乳清酸（5-FOA）抗性的突变靶点。我们鉴定出了一类新型突变体，它们能够在5-FOA存在的情况下生长。与[未提及的某类]突变体不同，[这类]突变体保持原养型，并且在没有尿嘧啶的情况下也能生长。除了对5-FOA有抗性外，我们还发现[基因名称]的突变也赋予了对5-氟胞嘧啶（5-FC）和5-氟尿嘧啶（5-FU）的抗性。我们总共在[基因名称]的32个残基上鉴定出了50个独特的错义突变。我们发现，32个受影响的残基中有28个位于[基因名称]与三种临床相关致病真菌之间保守的区域。这些发现表明，[基因名称]的突变呈现出利用5-FOA作为选择标记进行突变筛选的第二个靶点，以及对抗真菌治疗药物5-FC产生抗性的一种潜在模式。
