关键词: Antifungal Drug resistance Efflux pumps Proteome Stress response

来  源:   DOI:10.1007/s42770-024-01417-8

Abstract:
Fusarium oxysporum is a cross-kingdom pathogen that infects humans, animals, and plants. The primary concern regarding this genus revolves around its resistance profile to multiple classes of antifungals, particularly azoles. However, the resistance mechanism employed by Fusarium spp. is not fully understood, thus necessitating further studies to enhance our understanding and to guide future research towards identifying new drug targets. Here, we employed an untargeted proteomic approach to assess the differentially expressed proteins in a soil isolate of Fusarium oxysporum URM7401 cultivated in the presence of amphotericin B and fluconazole. In response to antifungals, URM7401 activated diverse interconnected pathways, such as proteins involved in oxidative stress response, proteolysis, and lipid metabolism. Efflux proteins, antioxidative enzymes and M35 metallopeptidase were highly expressed under amphotericin B exposure. Antioxidant proteins acting on toxic lipids, along with proteins involved in lipid metabolism, were expressed during fluconazole exposure. In summary, this work describes the protein profile of a resistant Fusarium oxysporum soil isolate exposed to medical antifungals, paving the way for further targeted research and discovering new drug targets.
摘要:
尖孢镰刀菌是一种感染人类的跨界病原体,动物,和植物。关于该属的主要关注围绕其对多种类型的抗真菌药的抗性,特别是唑类。然而,镰刀菌属的抗性机制。没有完全理解,因此,有必要进行进一步的研究,以增进我们的理解,并指导未来的研究,以确定新的药物靶点。这里,我们采用非靶向蛋白质组学方法评估了在两性霉素B和氟康唑存在下培养的尖孢镰刀菌URM7401土壤分离物中差异表达的蛋白质.为了应对抗真菌药,URM7401激活了各种相互连接的途径,如参与氧化应激反应的蛋白质,蛋白水解,和脂质代谢。外排蛋白,在两性霉素B暴露下,抗氧化酶和M35金属肽酶高表达。作用于有毒脂质的抗氧化蛋白,以及参与脂质代谢的蛋白质,在氟康唑暴露期间表达。总之,这项工作描述了暴露于医用抗真菌药物的抗性尖孢镰刀菌土壤分离物的蛋白质谱,为进一步的靶向研究和发现新的药物靶点铺平道路。
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