霍乱弧菌rmbb是一种具有破坏弧菌多糖生物膜活性的α-1,4-多糖裂解酶。

IF 4.9 1区 医学 Q1 MICROBIOLOGY PLoS Pathogens Pub Date : 2024-12-02 eCollection Date: 2024-12-01 DOI:10.1371/journal.ppat.1012750
Ranjuna Weerasekera, Alexis Moreau, Xin Huang, Kee-Myoung Nam, Alexander J Hinbest, Yun Huynh, Xinyu Liu, Christopher Ashwood, Lauren E Pepi, Eric Paulson, Lynette Cegelski, Jing Yan, Rich Olson
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引用次数: 0

摘要

许多致病菌形成生物膜是对环境和宿主危害的一种保护措施。生物膜基质的底层结构由分泌的大分子组成,通常包括胞外多糖。为了逃离生物膜,细菌可能产生许多基质降解酶,包括消化外多糖支架的糖苷酶。人类病原体霍乱弧菌聚集并分泌一种称为VPS(弧菌多糖)的外多糖,它在大多数情况下对生物膜的形成至关重要,由一个重复的四糖单位组成。先前的研究表明,一种名为rbbb的分泌糖苷酶参与了霍乱弧菌生物膜的扩散,尽管其发生的机制尚不清楚。为了探讨RbmB的功能问题,我们重组表达和纯化了RbmB,并测试了其对纯化VPS的活性。利用基于荧光的生化分析,我们发现在生理条件下,rmb在体外特异性切割VPS。利用质谱、固体核磁共振和溶液核磁共振对裂解过程进行分析表明,RbmB在特定位点(d-半乳糖和改性l -葡糖之间的α-1,4键)裂解VPS,使其成为四聚体和八聚体的混合物。我们证明了裂解产物在修饰的古鲁醛酸环上含有一个双键,这强烈表明rmbb是通过糖苷裂解酶机制进行裂解的。最后,我们发现来自霍乱弧菌和相关水生物种珊瑚弧菌的重组rmbb都能够破坏活的霍乱弧菌生物膜。我们的研究结果支持rmb作为参与生物膜分散的多糖裂解酶的作用,以及添加到潜在的治疗性抗菌酶工具箱中的另一种糖酵解酶。
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Vibrio cholerae RbmB is an α-1,4-polysaccharide lyase with biofilm-disrupting activity against Vibrio polysaccharide (VPS).

Many pathogenic bacteria form biofilms as a protective measure against environmental and host hazards. The underlying structure of the biofilm matrix consists of secreted macromolecules, often including exopolysaccharides. To escape the biofilm, bacteria may produce a number of matrix-degrading enzymes, including glycosidic enzymes that digest exopolysaccharide scaffolds. The human pathogen Vibrio cholerae assembles and secretes an exopolysaccharide called VPS (Vibrio polysaccharide) which is essential in most cases for the formation of biofilms and consists of a repeating tetrasaccharide unit. Previous studies have indicated that a secreted glycosidase called RbmB is involved in V. cholerae biofilm dispersal, although the mechanism by which this occurs is not understood. To approach the question of RbmB function, we recombinantly expressed and purified RbmB and tested its activity against purified VPS. Using a fluorescence-based biochemical assay, we show that RbmB specifically cleaves VPS in vitro under physiological conditions. Analysis of the cleavage process using mass spectrometry, solid-state NMR, and solution NMR indicates that RbmB cleaves VPS at a specific site (at the α-1,4 linkage between D-galactose and a modified L-gulose) into a mixture of tetramers and octamers. We demonstrate that the product of the cleavage contains a double bond in the modified guluronic acid ring, strongly suggesting that RbmB is cleaving using a glycoside lyase mechanism. Finally, we show that recombinant RbmB from V. cholerae and the related aquatic species Vibrio coralliilyticus are both able to disrupt living V. cholerae biofilms. Our results support the role of RbmB as a polysaccharide lyase involved in biofilm dispersal, as well as an additional glycolytic enzyme to add to the toolbox of potential therapeutic antibacterial enzymes.

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来源期刊
PLoS Pathogens
PLoS Pathogens MICROBIOLOGY-PARASITOLOGY
自引率
3.00%
发文量
598
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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