中北盐湖区内蒙古东部盐湖亚区放线菌资源勘探和新抗生素的发现

Due to the widely spread of the drug-resistance bacteria, new antibiotics are urgently needed. Actinomycetes are one of the most important antibiotics-producing pharmaceutical resources. Studies have shown that the posibility of discovery for new antibiotics from actinomycetes inhabited in special environments was higher. Saline lakes are special water-bodies with a relatively high concentration of dissolved salts. Previous studies have shown that actinomycetes from saline lakes is a potential resource for drugs discovery, since the actinomycetes from saline lakes are rich in diversity & novelty and a wide range of biological activities. Based on the previous studies on saline lake actinomycetes, the proposal is intended to dig actinomycetes as pharmaceutical resource collected in eastern Inner Mongolia subregion, north-central region of Chinese saline lakes with unique environmental factors, which has not been reported and few studied. Samples of sediments and soil from dried lake basin will be collected; actinomycetes including halophilic and halotolerant actinomycetes will be obtained by the method of pure culture; isolates will be analyzed by comparison of 16S rRNA gene sequences to explore the diversity and novelty of the culturable actinomycetes; the bioactive strains against drug-resistance bacteria will be selected by antimicrobial assay and screening of antibiotics biosynthetic genes; the novel actinobacteria species with bioactivity will be identified by the polyphasic taxonomic approaches and antibiotics will be purified and identified by the different chromatographies and the modern spectral techniques. The research aims will focus on discovery of new actinomycete species and new antibiotics, which will lay the foundation for drugs discovery.

细菌耐药形势严峻，亟待新型抗生素投入使用。以放线菌为主的药用微生物是抗生素的重要来源，研究表明从特殊环境放线菌中获得新型化合物的几率更大。盐湖是一种特殊的高盐生境，既往研究表明：盐湖放线菌物种多样、新资源丰富、生物活性广泛，是极具开发潜力的药物资源。在项目组前期盐湖放线菌研究的基础上，本项目选择环境独特、鲜有报道的我国中北盐湖区内蒙古东部盐湖亚区，采集盐湖沉积物和干涸湖盆的土壤，采用纯培养方法进行放线菌（包括耐盐、嗜盐放线菌）分离；通过16S rRNA 基因序列比对分析，探究其中可培养放线菌的物种多样性和新颖性；综合抗耐药菌活性及抗生素生物合成基因筛选，发现优质有潜力的放线菌药用资源；对具有抗耐药菌活性的新颖放线菌资源进行多相分类；利用色谱和波谱技术对优质药用菌株进行活性次级代谢产物的纯化和鉴定。本项目旨在发现新的放线菌资源、新的优质药用菌株和新型的活性化合物，为新抗生素的发现奠定基础。

细菌耐药形势严峻，亟待新型抗生素投入使用。以放线菌为主的药用微生物是抗生素的重要来源。盐湖是一种特殊的高盐生境，既往研究表明：盐湖来源放线菌物种多样、新资源丰富、生物活性广泛，是极具开发潜力的药物资源。. 本项目从锡林郭勒盟的高原盐湖中分离获得了隶属于8个目15个科28个属的365株放线菌，以链霉菌属和拟诺卡氏菌属为优势菌属。分离获得潜在新的放线菌分类单元28个，其中链霉菌新分类单元20个。链霉菌新颖性突出，15株链霉菌与有效发表菌株的16S rRNA基因的最高同源性低于98.0%。综合菌株的新颖性、抗菌活性和抗生素生物合成基因的检测结果，初步筛选出9株可用于进一步研究的药用菌株，其中4株对G+和G-病原菌均有明显活性。对菌株J5903和抗MRSA活性菌株XMNu-373进行了多相分类学鉴定。推荐菌株J5903为Planctomonas属新种，命名为Planctomonas psychrotolerans；推荐菌株XMNu-373为Phytoactinopolyspora属新种，命名为Phytoactinopolyspora mesophila。对潜在链霉菌新种XMNu-116的抗MRSA活性主产物进行了分离和鉴定，获得两个已知抗生素，Griseoviridin和Etamycin A。同时运用GNPS质谱分子网络及数据库比对预测到4个未知同系化合物。. 本项目对内蒙古东部盐湖亚区的主要分布地——锡林郭勒盟的高原盐湖中可培养放线菌资源的多样性、新颖性、抗菌活性、活性代谢产物进行了初步评价及分析。研究过程中储备了大量放线菌菌株，获得了多株优质抗菌药用放线菌菌种。研究结果揭示了该区域盐湖含有宝贵的药用放线菌菌种资源，丰富了我国盐湖药用放线菌资源的研究成果。本研究为盐湖来源新抗菌药物的研发储备了菌种资源和积累了理论基础。