
@article {230,
	title = {Termination of Poly--acetylglucosamine (PNAG) Polymerization with -Acetylglucosamine Analogues.},
	journal = {ACS Chem Biol},
	volume = {17},
	year = {2022},
	month = {2022 Nov 18},
	pages = {3036-3046},
	abstract = {<p>Bacteria require polysaccharides for structure, survival, and virulence. Despite their central role in microbiology, few tools are available to manipulate their production. In , the glycosyltransferase complex PgaCD produces poly--acetylglucosamine (PNAG), an extracellular matrix polysaccharide required for biofilm formation. We report that C6-substituted (H, F, N, SH, NH) UDP-GlcNAc substrate analogues are inhibitors of PgaCD. , the inhibitors cause PNAG chain termination, consistent with the mechanism of PNAG polymerization from the nonreducing terminus. , expression of the GlcNAc-1-kinase NahK in provided a non-native GlcNAc salvage pathway that produced the UDP-GlcNAc analogue inhibitors . The 6-fluoro and 6-deoxy derivatives were potent inhibitors of biofilm formation in the transformed strain, providing a tool to manipulate this key exopolysaccharide. Characterization of the UDP-GlcNAc pool and quantification of PNAG generation support PNAG termination as the primary mechanism of biofilm inhibition by 6-fluoro UDP-GlcNAc.</p>},
	keywords = {Acetylglucosamine, Biofilms, Escherichia coli, Polymerization, Uridine Diphosphate},
	issn = {1554-8937},
	doi = {10.1021/acschembio.1c00855},
	author = {Morrison, Zachary A and Eddenden, Alexander and Subramanian, Adithya Shankara and Howell, P Lynne and Nitz, Mark}
}
