恒河猴肠道细菌多样性及抗耐药肺炎病原菌放线菌资源初探

Pneumonia is one of the most common global childhood illnesses, and its mortality rate is the highest in infectious diseases. Bacterial infection is the leading cause of pneumonia. Colonization and reproduction of these pathogens are in connection with internal environment of host. Studies have showed that the intestinal microorganism played an important role in energy metabolism, metabolic disease and immunity. All these imply that gut microbiota impact the infection of pneumonia. And furthermore, aggravation of bacterial drug resistance makes people face a draconic reality, that is post-antibiotics era. Therefore, the discovery of novel antibiotics is extremely urgent. Intestinal actinobacteria as special microorganisms have gone into researchers’ eyes in the meantime.. In this study, Macaca mulatta chosen as the research model, the diversity of the gut bacteria was analyzed with metagenomic method based on 16S rRNA sequences to reveal the effect of intestinal flora on pneumonia infection. Pure culture and co-culture were utilized to screen the targeted actinobacterial strains. The active metabolites were obtained through the construction of HPLC-DAD fingerprint together with bioactivity-guided method. This work will contribute to deepening our understanding on the mechanism of pneumonic infection, and provide novel antibiotics with a good material foundation.

肺炎是世界上儿童死亡率最高的传染疾病。其发生原因主要是由细菌病原菌感染引起，这些致病菌的定殖与繁殖与宿主自身的集体环境有关。而研究显示，肠道微生物与人体的代谢机理及免疫调节有着密切联系。这意味着肠道微生物可能对肺炎的发生存在着影响。同时，抗生素的滥用使全球进入后抗生素时代，新型抗生素发掘工作迫在眉睫，肠道放线菌作为一类特境微生物资源，而逐步被研究者重视。. 本项目以健康和患肺炎的模式动物恒河猴为模型。利用16S rRNA宏基因组手段分析比较肠道系统群落的多样性，初步阐述肠道细菌对肺炎的影响。通过纯培养获得放线菌资源，并与病原菌共培养，针对性筛选抗耐药病原菌的菌株资源。建立代谢产物的HPLC-DAD指纹图库，结合活性追踪得到活性次级代谢产物。本项目的实施有利于加深对肺炎发病机理的认识，同时为抗耐药肺炎病原菌的新型抗生素的发掘提供物质基础。

肺炎是世界上儿童死亡率最高的传染疾病。其发生原因主要是由细菌病原菌感染引起，这些致病菌的定殖与繁殖与宿主自身的集体环境有关。而研究显示，肠道微生物与人体的代谢机 理及免疫调节有着密切联系。这意味着肠道微生物可能对肺炎的发生存在着影响。同时，抗生素的滥用使全球进入后抗生素时代，新型抗生素发掘工作迫在眉睫，肠道放线菌作为一类特境微生物资源，而逐步被研究者重视。 . 本项目以健康和患肺炎的模式动物恒河猴为模型。利用16S rRNA宏基因组手段分析比较肠道系统群落的多样性，初步阐述肠道细菌对肺炎的影响。通过纯培养获得放线菌资源，并且分离肺炎支原体的临床耐药菌株，针对性筛选抗耐药肺炎支原体的放线菌资源。同时筛选了抗耐药肺炎支原体的化合物。结果显示，大肠、直肠组群落极为相似，主要类群为厚壁菌门和拟杆菌门，而小肠与前两者群落构成显著不同，主要类群为变形菌门和厚壁菌门。大肠、直肠的微生物与小叶性肺炎可能存在相关性，而小肠微生物未发现存在相关性，同时各部位肠道微生物均未发现与大叶性肺炎存在相关性。分离得到83株放线菌，59株肺炎支原体菌株并做了耐药检测，耐药率达到80%。对9株经典放线菌进行抗耐药肺炎支原体活性筛选，得到2株活性较好的菌株。另外筛选了256个化合物，筛到9个具有良好抗耐药肺炎支原体的化合物。. 本项目的实施有利于加深对肺炎发病机理及肠道微生物功能的认识，同时为抗 耐药肺炎病原菌的新型抗生素的发掘提供物质基础。.