Ouyang Xudong, Hoeksma Jelmer, Beenker Wouter A G, van der Beek Samantha, den Hertog Jeroen
Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, Netherlands.
Institute Biology Leiden, Leiden University, Leiden, Netherlands.
Front Microbiol. 2024 Jan 29;15:1332774. doi: 10.3389/fmicb.2024.1332774. eCollection 2024.
The thermophilic fungus is a saprobe that is commonly isolated from soil. Here, we identified a Gram-positive bacteria-selective antimicrobial secondary metabolite from this fungal species, harzianic acid (HA). Using strain 168 combined with dynamic bacterial morphology imaging, we found that HA targeted the cell membrane. To further study the antimicrobial activity of HA, we isolated an HA-resistant strain, strain M9015, and discovered that the mutant had more translucent colonies than the wild type strain, showed cross resistance to rifampin, and harbored five mutations in the coding region of four distinct genes. Further analysis of these genes indicated that the mutation in might be responsible for the translucency of the colonies, and mutation in for resistance to both HA and rifampin. We conclude that HA is an antimicrobial agent against Gram-positive bacteria that targets the cell membrane.
嗜热真菌是一种腐生菌，通常从土壤中分离得到。在此，我们从该真菌物种中鉴定出一种革兰氏阳性菌选择性抗菌次生代谢产物——哈茨酸（HA）。使用168菌株结合动态细菌形态成像，我们发现HA靶向细胞膜。为了进一步研究HA的抗菌活性，我们分离出一株HA抗性菌株M9015，发现该突变体的菌落比野生型菌株更半透明，对利福平表现出交叉抗性，并在四个不同基因的编码区存在五个突变。对这些基因的进一步分析表明，[此处原文缺失基因名称]中的突变可能导致菌落半透明，而[此处原文缺失基因名称]中的突变导致对HA和利福平均产生抗性。我们得出结论，HA是一种针对革兰氏阳性菌且靶向细胞膜的抗菌剂。
