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.
