CAREER: Essential Functions of Secondary Metabolic Networks for Bacterial Competition

智力价值虽然次生代谢物是被认为对生存不必要的有机化合物，但众所周知，细菌产生这些化合物是为了发挥重要的特殊功能。一些次生代谢物抑制或摧毁竞争对手。其他的是控制细胞状态之间的转换的信号，比如生物膜的形成和蜂群。对次生代谢物的传统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，这选择了强大的竞争机制。因此，次生代谢物网络如何在物种之间的竞争中发挥作用的问题并没有用这种传统的方法来解决。这个NSF职业项目的重点是研究混合物种培养，以扩大可检测到的生物活性代谢物的范围及其竞争功能。根据初步数据，表明枯草芽孢杆菌和链霉菌之间存在几种分泌代谢物的交换。微生物遗传学结合生理和发育分析将被用来确定化合物在这两个物种之间争夺有限资源的竞争中的作用。此外，代谢活性的研究将与创新的成像质谱学相结合，以评估多种活性代谢物的净影响。还将确定有助于产生次生代谢物的物种竞争成功的分泌酶。这个项目将为细菌竞争中的次生代谢网络提供一个新的视角。广泛的影响本项目的研究目标与教育和推广计划交织在一起，以提高公众对抗生素的自然来源的认识和理解，抗生素是微生物的次生代谢产物，以及它们的代谢。该教育计划将通过侧重于微生物相互作用的课程作业和实验室研究，产生和传播关于细菌生态学、新陈代谢和次生代谢物合成的基本知识，并强调从单一病原体到公共生物体对细菌的看法的变化。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，因此与外联计划相结合，该计划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.