Li Qiqi, Wang Zhou, Jiang Cuiping, Yin Jianglin, Liu Yonghong, Qu Xinjian, Yi Xiangxi, Gao Chenghai
Institute of Marine Drugs/Faculty of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, China.
Guangxi Key Laboratory of Marine Drugs/Guangxi University Engineering Research Center of High-Efficient Utilization of Marine Traditional Chinese Medicine Resources, Guangxi University of Chinese Medicine, Nanning 530200, China.
Mar Drugs. 2025 Feb 10;23(2):76. doi: 10.3390/md23020076.
(TM) is an opportunistic pathogenic fungus that mainly infects immunocompromised patients. Currently, the global prevalence of talaromycosis caused by TM is increasing, leading to an increased demand for anti-TM drugs. In our previous study, a novel 28-membered macrolide compound, antifungalmycin B (ANB), was isolated from GXIMD 06359, exhibiting significant antifungal properties. However, its in vivo mechanisms and direct antifungal effects warrant further investigation. In this study, we employed a mouse model in conjunction with transcriptomic and proteomic approaches to explore the antifungal activity of ANB against . In an in vivo mouse model infected with infection, ANB significantly reduced fungal burdens in the liver, spleen, lungs, and kidneys. Additionally, it markedly decreased the levels of reactive oxygen species (ROS) and cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Proteomic and transcriptomic studies, complemented by parallel reaction monitoring (PRM) analysis, revealed that ANB effectively disrupted acid biosynthesis and cellular energy metabolism, thereby impairing mitochondrial functions in . These effects were exerted through multiple pathways. These findings highlight the potential of ANB as a versatile inhibitor of polyene macrolide-resistant fungi, offering a promising therapeutic avenue for the treatment of talaromycosis.
土曲霉（TM）是一种机会致病性真菌，主要感染免疫功能低下的患者。目前，由TM引起的土曲霉病在全球的患病率正在上升，导致对抗TM药物的需求增加。在我们之前的研究中，从GXIMD 06359中分离出一种新型的28元大环内酯化合物，抗真菌霉素B（ANB），它具有显著的抗真菌特性。然而，其体内作用机制和直接抗真菌作用仍有待进一步研究。在本研究中，我们采用小鼠模型结合转录组学和蛋白质组学方法，探讨ANB对土曲霉的抗真菌活性。在感染土曲霉的体内小鼠模型中，ANB显著降低了肝脏、脾脏、肺和肾脏中的真菌负荷。此外，它还显著降低了活性氧（ROS）和细胞因子的水平，包括白细胞介素（IL）-1β、IL-6和肿瘤坏死因子（TNF）-α。蛋白质组学和转录组学研究，辅以平行反应监测（PRM）分析，表明ANB有效地破坏了酸生物合成和细胞能量代谢，从而损害了土曲霉的线粒体功能。这些作用是通过多种途径发挥的。这些发现突出了ANB作为一种多烯大环内酯耐药真菌通用抑制剂的潜力，为土曲霉病的治疗提供了一条有前景的治疗途径。
