Object's details: Preference of bacterial rhamnosyltransferases for 6‑deoxysugars reveals a strategy to deplete O‑antigens

Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
Preference of bacterial rhamnosyltransferases for 6‑deoxysugars reveals a strategy to deplete O‑antigens
Creator:
Harnagel, Alexa P.;
Sheshova, Mia;
Zheng, Meng;
Zheng, Maggie;
Skorupinska-Tudek, Karolina;
Swiezewska, Ewa;
Lupoli, Tania J.
Description:
Bacteria synthesize hundreds of bacteria-specific or “rare” sugars that are absent in mammalian cells and enriched in 6-deoxy monosaccharides such as L-rhamnose (L-Rha). Across bacteria, L-Rha is incorporated into glycans by rhamnosyltransferases (RTs) that couple nucleotide sugar substrates (donors) to target biomolecules (acceptors). Since L-Rha is required for the biosynthesis of bacterial glycans involved in survival or host infection, RTs represent potential antibiotic or antivirulence targets. However, purified RTs and their unique bacterial sugar substrates have been difficult to obtain. Here, we use synthetic nucleotide rare sugar and glycolipid analogs to examine substrate recognition by three RTs that produce cell envelope components in diverse species, including a known pathogen. We find that bacterial RTs prefer pyrimidine nucleotide-linked 6-deoxysugars, not those containing a C6-hydroxyl, as donors. While glycolipid acceptors must contain a lipid, isoprenoid chain length, and stereochemistry can vary. Based on these observations, we demonstrate that a 6-deoxysugar transition state analog inhibits an RT in vitro and reduces levels of RT-dependent O-antigen polysaccharides in Gram-negative cells. As O-antigens are virulence factors, bacteria-specific sugar transferase inhibition represents a novel strategy to prevent bacterial infections.
Object availability:
free access
Date:
2023
Type:
Article;
PeerReviewed
Language:
English
Format:
application/pdf
Publisher:
ACS Publications
Relation: http://eprints.ibb.waw.pl/2307 ;https://pubs.acs.org/doi/10.1021/jacs.3c03005 ;doi: 10.1021/jacs.3c03005
Subject:
QH301 Biology
Identifier: http://eprints.ibb.waw.pl/2307/1/2023_JACS_Skorupinska.pdf ;
Harnagel, Alexa P. and Sheshova, Mia and Zheng, Meng and Zheng, Maggie and Skorupinska-Tudek, Karolina and Swiezewska, Ewa and Lupoli, Tania J. (2023) Preference of bacterial rhamnosyltransferases for 6‑deoxysugars reveals a strategy to deplete O‑antigens. Journal of American Chemical Society, 145 . pp. 15639-15646.
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

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Object's details: Preference of bacterial rhamnosyltransferases for 6‑deoxysugars reveals a strategy to deplete O‑antigens

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