CAREER: Essential Functions of Secondary Metabolic Networks for Bacterial Competition

智力优势虽然次级代谢产物是被认为是生存所必需的有机化合物，但已知细菌会产生这些化合物以实现重要的专门功能。 一些次级代谢物抑制或破坏竞争对手。 其他是控制细胞状态之间转换的信号，例如生物膜形成和群集。 传统的次级代谢物研究涉及纯化的分子，这些分子在分离的物种上进行测试。 然而，细菌主要存在于复杂的多物种群落中，这些群落选择强大的竞争机制。 因此，这种传统方法无法解决次级代谢物网络在物种间竞争中如何发挥作用的问题。 这个NSF CAREER项目的重点是研究混合物种的文化，扩大了可检测的生物活性代谢物及其竞争功能的范围。 根据初步数据表明，几个分泌的代谢产物之间交换枯草芽孢杆菌和链霉菌属Mg1，微生物遗传学结合生理和发育分析将被用来确定这两个物种之间的竞争有限的资源的化合物的作用。 此外，代谢活性的研究将与创新的成像质谱法相结合，以评估多种活性代谢物的净影响。 还将鉴定有助于产生次级代谢产物的物种竞争成功的分泌酶。 该项目将为细菌竞争中的次级代谢网络提供一个新的视角。更广泛的影响该项目的研究目标与教育和推广计划交织在一起，以促进公众对抗生素天然来源（微生物次级代谢产物）及其代谢的认识和理解。 该教育计划将通过课程和实验室研究产生和传播细菌生态学，代谢和次级代谢产物合成的基本知识，这些课程和实验室研究侧重于微生物相互作用，并强调从单一病原体到公共生物体的细菌变化观点。 课程还包括数据库开发和学生和公众可访问的基于网络的界面，因此与外联方案相结合，将向更广泛的受众传达相同的基本知识。

Intellectual MeritWhile secondary metabolites are organic compounds that are considered to be nonessential for survival, bacteria are known to produce these compounds for important specialized functions. Some secondary metabolites inhibit or destroy competitors. Others are signals to control transitions between cellular states, such as biofilm formation and swarming. Traditional studies of secondary metabolites involve purified molecules that are tested on isolated species. However, bacteria predominantly exist in complex multi-species communities, which select for robust competitive mechanisms. Therefore the question as to how networks of secondary metabolites function in the competition between species is not addressed by such traditional approaches. This NSF CAREER project focuses on examining mixed-species cultures that expands the range of detectable bioactive metabolites and their competitive functions. Based on preliminary data that indicate several secreted metabolites are exchanged between Bacillus subtilis and Streptomyces sp. Mg1, microbial genetics in combination with physiological and developmental analyses will be used to determine the role of the compounds in the competition between these two species for limited resources. Further, studies of metabolic activity will be integrated with innovative imaging mass spectrometry to assess the net impact of multiple active metabolites. Secreted enzymes that contribute to the competitive success of the species producing the secondary metabolites will also be identified. This project will provide a new view of secondary metabolic networks in bacterial competition.Broader ImpactsThe research goals of this project are interwoven with education and outreach programs to promote public awareness and understanding of natural sources of antibiotics, which are microbial secondary metabolites, and their metabolism. The education program will produce and disseminate basic knowledge of bacterial ecology, metabolism, and synthesis of secondary metabolites via coursework and laboratory studies that focus on microbial interactions and emphasize a changing perspective on bacteria from single pathogenic entities to communal organisms. The coursework also includes database development and web-based interfaces accessible to students and the public, and so is integrated with the outreach program, which will convey the same basic knowledge to wider audiences.