Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Microbiology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection (Guangxi Normal University), Ministry of Education, Guilin, China.
mSphere. 2020 Oct 7;5(5):e00771-20. doi: 10.1128/mSphere.00771-20.
The rise of drug resistance in fungal pathogens is becoming a serious problem owing to the limited number of antifungal drugs available. Identifying and targeting factors essential for virulence or development unique to fungal pathogens is one approach to develop novel treatments for fungal infections. In this study, we present the identification and functional characterization of a novel developmental regulator in , AfMed15, which contained a conserved Med15_fungal domain, as determined by screening of a mutant library that contained more than 2,000 hygromycin-resistant transformants. Downregulating the expression of abolished the conidiation and decreased the fungal virulence in an insect model. Strikingly, the overexpression of caused fungal death accompanied by intensive autophagy. RNA sequencing of an overexpression strain revealed that altered gene expression patterns were associated with carbon metabolism, energy metabolism, and translation. Interestingly, the addition of metal ions could partially rescue fungal death caused by the overexpression of , indicating that disordered ion homeostasis is a potential reason for the fungal death caused by the overexpression of Considering that the precise expression of is crucial for fungal development, virulence, and survival and that no ortholog was found in humans, is an ideal target for antifungal-drug development. The identification and characterization of regulators essential for virulence or development constitute one approach for antifungal drug development. In this study, we screened and functionally characterized , a novel developmental regulator in We demonstrate that the precise transcriptional expression of is crucial for fungal asexual development, virulence, and survival. Downregulating the expression of abolished the conidiation and decreased the fungal virulence in an insect model. In contrast, the overexpression of caused fungal death accompanied by intensive autophagy. Our study provides a foundation for further studies to identify compounds perturbing the expression of that may be used for the prevention of invasive infections.
由于可用的抗真菌药物数量有限,真菌病原体的耐药性上升正在成为一个严重的问题。确定和针对真菌病原体特有的毒力或发育所必需的因素是开发新型真菌感染治疗方法的一种方法。在这项研究中,我们通过筛选包含超过 2000 个潮霉素抗性转化子的突变体文库,鉴定并功能表征了真菌中的一种新型发育调节剂 AfMed15。该文库包含超过 2000 个潮霉素抗性转化子。下调 的表达会导致分生孢子形成减少,并降低昆虫模型中的真菌毒力。令人惊讶的是, 的过表达导致真菌死亡,并伴有强烈的自噬。对 过表达菌株的 RNA 测序表明,改变的基因表达模式与碳代谢、能量代谢和翻译有关。有趣的是,添加金属离子可以部分挽救由 过表达引起的真菌死亡,表明紊乱的离子稳态是由 过表达引起的真菌死亡的一个潜在原因。考虑到 的精确表达对真菌发育、毒力和存活至关重要,并且在人类中没有发现同源物,因此 是开发抗真菌药物的理想靶点。筛选和鉴定对毒力或发育至关重要的调节剂是开发抗真菌药物的一种方法。在这项研究中,我们筛选并功能表征了 ,这是一种新型发育调节剂。我们证明了 的精确转录表达对真菌无性发育、毒力和存活至关重要。下调 的表达会导致分生孢子形成减少,并降低昆虫模型中的真菌毒力。相比之下, 的过表达会导致真菌死亡,并伴有强烈的自噬。我们的研究为进一步研究确定扰乱 的表达的化合物提供了基础,这些化合物可能用于预防侵袭性 感染。