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Progress and prospects for small-molecule probes of bacterial imaging

Abstract

Fluorescence microscopy is an essential tool for the exploration of cell growth, division, transcription and translation in eukaryotes and prokaryotes alike. Despite the rapid development of techniques to study bacteria, the size of these organisms (1–10 μm) and their robust and largely impenetrable cell envelope present major challenges in imaging experiments. Fusion-based strategies, such as attachment of the protein of interest to a fluorescent protein or epitope tag, are by far the most common means for examining protein localization and expression in prokaryotes. While valuable, the use of genetically encoded tags can result in mislocalization or altered activity of the desired protein, does not provide a readout of the catalytic state of enzymes and cannot enable visualization of many other important cellular components, such as peptidoglycan, lipids, nucleic acids or glycans. Here, we highlight the use of biomolecule-specific small-molecule probes for imaging in bacteria.

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Figure 1: Genetically encoded tags for bacterial imaging.
Figure 2: Schematic representation of bacterial peptidoglycan (PG).
Figure 3: Antibiotic-inspired probes and images obtained with these compounds.
Figure 4: Peptidoglycan-inspired probes and images obtained with these compounds.
Figure 5: Carbohydrate-inspired and turnover-dependent probe designs.

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Acknowledgements

This work was supported by NIH DP2OD008592 (E.E.C.), a Pew Biomedical Scholar Award (E.E.C.), Sloan Research Fellow Award (E.E.C.) and Indiana University–Bloomington Department of Chemistry Start-Up Funds and a Marvin Carmack Fellowship (O.K.).

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Kocaoglu, O., Carlson, E. Progress and prospects for small-molecule probes of bacterial imaging. Nat Chem Biol 12, 472–478 (2016). https://doi.org/10.1038/nchembio.2109

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