基于可视化质谱技术从特境真菌中发掘新型抗CRAB活性分子

鲍曼不动杆菌耐药问题日益严峻，其中碳青霉烯类耐药鲍曼不动杆菌（CRAB）已被世界卫生组织列为严重威胁人类健康的头号耐药细菌；而与之相对，治疗CRAB感染的药物严重匮乏，亟需研发新型抗生素。特殊生境真菌独特的代谢途径和新颖的化学结构使其逐渐成为发现新型活性分子的重要资源。本项目前期从1140份特境（西藏）真菌发酵液中筛选出4株抗CRAB活性显著的真菌，在此基础上，拟通过可视化质谱技术对活性菌株的代谢产物进行分析，并通过jupyter notebook将活性结果引入可视化质谱结果中，用于指导活性分子的确定，结合GNPS和模拟质谱库进行分析排重，从而确定潜在新活性分子，进而对其进行分离、纯化和结构鉴定，最终将确定的新单体化合物进行活性评价以及成药性研究，以期获得新型抗CRAB活性的天然产物，为对抗日益严峻的CRAB感染提供更多先导化合物。

The drug resistance of Acinetobacter baumannii is becoming more and more serious. The one of them, the carbapenem-resistant Acinetobacter baumannii (CRAB) has been listed by the World Health Organization as the number one drug-resistant bacteria that seriously threatens human health. In contrast, the drugs for treating CRAB infections are severely lacking, and there is an urgent need to develop novel antibiotics. The unique metabolic pathways and novel chemical structures of fungi in unique habitant have gradually made them as an important resource for discovering new active molecules. In our previous study, 4 strains with significant anti-CRAB activity were screened from 1140 fermentation broths of unique habitant (Tibet) fungi. On this basis, the metabolites of the active strains were analyzed by visual mass spectrometry technology. The activity results were added into the results of visual mass spectrometry though jupyter notebook to guide the determination of active molecules. Combine with GNPS and in silico MS to analyze and dereplication, determine potential novel active molecules, and then, isolate, purify and identify the potential novel active molecules, evaluate their activity and research druggability. It is hoped that the novel anti-CRAB natural products in the four active strains will be discovered through the visualization of mass spectrometry technology, and more lead compounds will be provided to solve the increasingly severe CRAB infection.