Issue 8, 2024

Advances and prospects of analytic methods for bacterial transglycosylation and inhibitor discovery

Abstract

The cell wall is essential for bacteria to maintain structural rigidity and withstand external osmotic pressure. In bacteria, the cell wall is composed of peptidoglycan. Lipid II is the basic unit for constructing highly cross-linked peptidoglycan scaffolds. Transglycosylase (TGase) is the initiating enzyme in peptidoglycan synthesis that catalyzes the ligation of lipid II moieties into repeating GlcNAc-MurNAc polysaccharides, followed by transpeptidation to generate cross-linked structures. In addition to the transglycosylases in the class-A penicillin-binding proteins (aPBPs), SEDS (shape, elongation, division and sporulation) proteins are also present in most bacteria and play vital roles in cell wall renewal, elongation, and division. In this review, we focus on the latest analytical methods including the use of radioactive labeling, gel electrophoresis, mass spectrometry, fluorescence labeling, probing undecaprenyl pyrophosphate, fluorescence anisotropy, ligand-binding-induced tryptophan fluorescence quenching, and surface plasmon resonance to evaluate TGase activity in cell wall formation. This review also covers the discovery of TGase inhibitors as potential antibacterial agents. We hope that this review will give readers a better understanding of the chemistry and basic research for the development of novel antibiotics.

Graphical abstract: Advances and prospects of analytic methods for bacterial transglycosylation and inhibitor discovery

Article information

Article type
Critical Review
Submitted
13 ноя 2023
Accepted
06 мар 2024
First published
08 мар 2024

Analyst, 2024,149, 2204-2222

Advances and prospects of analytic methods for bacterial transglycosylation and inhibitor discovery

T. Hsu and J. Fang, Analyst, 2024, 149, 2204 DOI: 10.1039/D3AN01968C

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