Isolation of New Antibiotics From Soil Microorganisms

描述（由申请人提供）：本项目有两个主要目标：(1)从天然来源（土壤微生物）中鉴定和分离新型抗菌化合物，(2)培养学生结合微生物学和有机化学的综合研究方法。抗生素化疗越来越受到抗生素耐药菌株进化的影响，需要新的抗生素化合物来取代或补充目前使用的抗生素化合物。许多常用抗生素的原始来源是土壤微生物。这个项目继续寻找从广泛地点收集的土壤样本中分泌新化合物的细菌。将采用不同的实验室生长条件来扩大从这些样品培养的生物类型的范围，包括厌氧和营养有限的培养基。产生抑制化学物质的细菌种类将在混合竞争培养中鉴定，然后在纯培养中分离和生长。这些候选抗生素生产商的身份将通过标准微生物分型程序确定，并辅以分子技术（PFGE）。从这些纯培养物中提取条件培养基，通过标准和高效液相色谱法提取和纯化活性抗菌化合物。这些化合物的组成和结构将使用光谱技术确定，并将结果与已知的抗菌剂进行比较。新化合物将成为后续工作（此处未描述）确定这些药物用于疾病化疗的有用性的候选者。

DESCRIPTION (provided by applicant): This project has two main goals: (1) to identify and isolate novel antibacterial compounds from natural sources (soil microorganisms), and (2) to train students in integrative approaches to research, combining microbiology and organic chemistry. Antibiotic chemotherapy has been increasingly compromised by the evolution of antibiotic resistant strains, and new antibiotic compounds are needed to replace or supplement those in current use. The original sources of many common antibiotics were soil microorganisms. This project continues that hunt, seeking bacteria that secrete novel compounds from soil samples collected from a wide range of sites. Varied laboratory growth conditions will be employed to extend the range of types of organisms cultured from these samples, including anaerobiosis and nutrient limited media. Bacterial species producing inhibitory chemicals will be identified in mixed competition cultures, then isolated and grown in pure cultures. The identity of these candidate antibiotic-producers will be determined by standard microbiological typing procedures, supplemented with molecular techniques (PFGE). Conditioned media from these pure cultures will be treated to extract and purify the active antibacterial compounds by standard and HPLC-based chromatography. The composition and structure of these compounds will be determined using spectroscopic techniques, and the results compared with known antibacterial agents. Novel compounds will be candidates for later work (not described here) determining the usefulness of these agents for disease chemotherapy. Student researchers participating in this project will experience the integration of fields normally taught as separate disciplines. Their continued success as scientists, and their contributions to advancements in human health will be enhanced by a multidisciplinary approach to research.