CAREER: Chemical Tools for Understanding the Mycomembrane of the Corynebacterineae

有了这个奖项，化学部门的生命过程化学项目资助了中密歇根大学的Benjamin Swarts博士，以研究棒状杆菌亚目中数百种细菌中存在的独特细胞膜的结构和动力学。所有细菌都有一层或两层膜的细胞包膜，这些膜在细胞防御、通讯和结构完整性中起着关键作用。棒状杆菌科的物种有两层膜，最外层主要由称为霉菌酸缀合物的复杂糖链脂质组成。这种“菌膜”是棒状杆菌科所特有的，并赋予它们独特的生理和致病特性。由于使用标准实验技术时遇到的挑战，许多方面的生产，维护和菌膜的组成仍然未知。该项目产生并利用新的化学生物学工具来表征菌膜的结构和动力学。正在开发的工具是更好地了解棒状杆菌如何在周围环境中生存和适应的过程的重要组成部分。此外，对这种细菌系统的研究促进了对细菌与环境相互作用本质的理解，并提供了有助于加强病原体环境控制的信息。从事本研究的本科生和博士后在有机合成、微生物学和蛋白质组学方面接受跨学科培训。这项研究也被纳入了一个向社区大学学生介绍化学细菌学研究并鼓励他们继续接受科学教育的推广计划。该项目产生的工具有望具有广泛的效用，并支持其他科学家进行棒状杆菌科的基础和应用研究。传统的生物化学和分子生物学方法不适合研究菌膜，因为它主要由非遗传编码的脂质和糖组成。本研究项目开发化学探针，利用天然代谢途径将标签引入完整细菌细胞中的特定菌膜成分。然后根据实验目的，对标记的分子进行成像或质谱鉴定。该项目中开发的探针提供了以下信息：(i)当细菌遇到压力时，菌膜的主要糖脂成分是如何合成和重塑的；（ii）哪些蛋白质存在于菌丝膜中，并对菌丝膜的构建和维持起作用。该项目的研究结果将有助于提高对菌膜结构和动力学的理解，并为棒状杆菌亚目细菌的生理学提供见解。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Benjamin Swarts at Central Michigan University to investigate the structure and dynamics of a unique cell membrane present in hundreds of bacterial species of the suborder Corynebacterineae. All bacteria have cell envelopes with one or two membranes that play critical roles in cellular defense, communication, and structural integrity. Species in the Corynebacterineae have two membranes, the outermost of which is composed mostly of complex sugar-linked lipids called mycolic acid conjugates. This "mycomembrane" is unique to the Corynebacterineae and gives them distinctive physiological and pathogenic characteristics. Many aspects of the production, maintenance, and composition of the mycomembrane remain unknown because of the challenges encountered when using standard experimental techniques. This project generates and utilizes new chemical biology tools to characterize the structure and dynamics of the mycomembrane. The tools being developed form a significant part of the process of acquiring a better understanding of how the Corynebacterineae survive within and adapt to their surrounding environment. In addition, an investigation of this bacterial system advances understanding of the nature of interactions of bacteria with the environment and provides information that would enhance efforts to gain environmental control of pathogens. Undergraduate students and postdoctoral fellows working on this research acquire interdisciplinary training in organic synthesis, microbiology and proteomics. This research is also integrated into an outreach program that introduces community college students to chemical bacteriology research and encourages their continued education in science. The tools generated in this project are expected to have broad utility and to support other scientists pursuing basic and applied research on the Corynebacterineae.Traditional biochemical and molecular biological approaches are not well-suited to investigating the mycomembrane because it is made up largely of non-genetically encoded lipids and sugars. This research project develops chemical probes that exploit native metabolic pathways to introduce tags into specific mycomembrane components in intact bacterial cells. Tagged molecules are then imaged or identified by mass spectrometry, depending on the goal of the experiment. The probes developed in this project provide information on (i) how the major glycolipid constituents of the mycomembrane are synthesized and remodeled when the bacterium encounters stress; and (ii) what proteins reside within and contribute to the construction and maintenance of the mycomembrane. The findings from this project will lead to an improved understanding of mycomembrane structure and dynamics and provide insight into the physiology of bacteria in the Corynebacterineae suborder.