Biosynthesis of Salmonella O43 and Escherichia coli O86 antigens: Comparison of α1,3-GalNAc-transferases WfbG and WbnH

IF 2.4 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Carbohydrate Research Pub Date : 2025-02-22 DOI:10.1016/j.carres.2025.109434

D. Falconer, K. Phillippopoulos, D. Czuchry, A. Kocev, I. Brockhausen

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Abstract

Antibiotic resistance is on the rise, making bacterial infections an increasing threat to human health. O-antigenic polysaccharides are important virulence factors of pathogenic Gram-negative bacteria that can be involved in immune evasion and colonization. The O antigens of enteropathogenic Salmonella enterica O43 (SO43) and Escherichia coli O86 (ECO86) are structurally similar and contain a mimic of the blood group B determinant. However, the SO43 O antigen repeating unit has GlcNAc at the reducing end while ECO86 contains a GalNAc residue. To explore this difference we characterized the α1,3-GalNAc-transferase responsible for the addition of GalNAc to GalNAc-PP-undecaprenol in ECO86 (WbnH) and the enzyme proposed to add GalNAc to GlcNAc-PP-undecaprenol in SO43 (WfbG). Substrate specificity study of these GT4 enzymes showed a strict donor specificity for UDP-GalNAc. However, WfbG could use either GlcNAcα- or GalNAcα-PP-phenylundecyl as a natural acceptor substrate analog whereas WbnH was only active with GalNAcα-PP-phenylundecyl. The GlcNAc-PP-undecaprenol 4-epimerase gene in the ECO86 strain can provide the essential acceptor substrate for WbnH. These data help to explain the difference in O antigen structures between SO43 and ECO86. A series of GT4 enzymes was analyzed by bioinformatics to identify common sequences that help to predict their functions. Characterization of these bacterial GTs can identify potential targets to disrupt virulence mechanisms.

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来源期刊

Carbohydrate Research 化学-生化与分子生物学

CiteScore

5.00

自引率

3.20%

发文量

183

审稿时长

3.6 weeks

期刊介绍： Carbohydrate Research publishes reports of original research in the following areas of carbohydrate science: action of enzymes, analytical chemistry, biochemistry (biosynthesis, degradation, structural and functional biochemistry, conformation, molecular recognition, enzyme mechanisms, carbohydrate-processing enzymes, including glycosidases and glycosyltransferases), chemical synthesis, isolation of natural products, physicochemical studies, reactions and their mechanisms, the study of structures and stereochemistry, and technological aspects. Papers on polysaccharides should have a "molecular" component; that is a paper on new or modified polysaccharides should include structural information and characterization in addition to the usual studies of rheological properties and the like. A paper on a new, naturally occurring polysaccharide should include structural information, defining monosaccharide components and linkage sequence. Papers devoted wholly or partly to X-ray crystallographic studies, or to computational aspects (molecular mechanics or molecular orbital calculations, simulations via molecular dynamics), will be considered if they meet certain criteria. For computational papers the requirements are that the methods used be specified in sufficient detail to permit replication of the results, and that the conclusions be shown to have relevance to experimental observations - the authors'' own data or data from the literature. Specific directions for the presentation of X-ray data are given below under Results and "discussion".