Shedding Light on Bacterial Physiology with Click Chemistry

Abstract

Bacteria constitute a major lifeform on this planet and play numerous roles in ecology, physiology, and human disease. However, conventional methods to probe their activities are limited in their ability to visualize and identify their functions in these diverse settings. In the last two decades, the application of click chemistry to label these microbes has deepened our understanding of bacterial physiology. With the development of a plethora of chemical tools that target many biological molecules, it is possible to track these microorganisms in real-time and at unprecedented resolution. Here, we review click chemistry, including bioorthogonal reactions, and their applications in imaging bacterial glycans, lipids, proteins, and nucleic acids using chemical reporters. We also highlight significant advances that have enabled biological discoveries that have heretofore remained elusive.

Selective Glycan Labeling of Mannose-Containing Glycolipids in Mycobacteria

“…Because glycan biosynthesis is not directly genetically encoded, installing labels through genetic manipulation is difficult . Metabolic incorporation offers an incisive route to installing handles into glycans. − The process involves multistep, intracellular processing of simple monosaccharide building blocks by endogenous metabolic machinery, culminating in the presentation of the end products on the cell surface . Though several successful examples have been demonstrated in bacteria, applying this strategy in these organisms poses challenges due to the complexity of glycan metabolism and catabolism in bacteria. ,,− …”