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Insights on Pseudomonas aeruginosa Carbohydrate Binding from Profiles of Cystic Fibrosis Isolates Using Multivalent Fluorescent Glycopolymers Bearing Pendant Monosaccharides
Microorganisms ( IF 4.5 ) Pub Date : 2024-04-16 , DOI: 10.3390/microorganisms12040801
Deborah L. Chance 1, 2 , Wei Wang 3 , James K. Waters 4 , Thomas P. Mawhinney 2, 3, 4
Affiliation  

Pseudomonas aeruginosa contributes to frequent, persistent, and, often, polymicrobial respiratory tract infections for individuals with cystic fibrosis (CF). Chronic CF infections lead to bronchiectasis and a shortened lifespan. P. aeruginosa expresses numerous adhesins, including lectins known to bind the epithelial cell and mucin glycoconjugates. Blocking carbohydrate-mediated host–pathogen and intra-biofilm interactions critical to the initiation and perpetuation of colonization offer promise as anti-infective treatment strategies. To inform anti-adhesion therapies, we profiled the monosaccharide binding of P. aeruginosa from CF and non-CF sources, and assessed whether specific bacterial phenotypic characteristics affected carbohydrate-binding patterns. Focusing at the cellular level, microscopic and spectrofluorometric tools permitted the solution-phase analysis of P. aeruginosa binding to a panel of fluorescent glycopolymers possessing distinct pendant monosaccharides. All P. aeruginosa demonstrated significant binding to glycopolymers specific for α-D-galactose, β-D-N-acetylgalactosamine, and β-D-galactose-3-sulfate. In each culture, a small subpopulation accounted for the binding. The carbohydrate anomeric configuration and sulfate ester presence markedly influenced binding. While this opportunistic pathogen from CF hosts presented with various colony morphologies and physiological activities, no phenotypic, physiological, or structural feature predicted enhanced or diminished monosaccharide binding. Important to anti-adhesive therapeutic strategies, these findings suggest that, regardless of phenotype or clinical source, P. aeruginosa maintain a small subpopulation that may readily associate with specific configurations of specific monosaccharides. This report provides insights into whole-cell P. aeruginosa carbohydrate-binding profiles and into the context within which successful anti-adhesive and/or anti-virulence anti-infective agents for CF must contend.

中文翻译:

使用带有单糖侧链的多价荧光糖聚合物从囊性纤维化分离株的剖面中洞察铜绿假单胞菌碳水化合物的结合

铜绿假单胞菌会导致囊性纤维化 (CF) 患者发生频繁、持续且常常是多种微生物的呼吸道感染。慢性 CF 感染会导致支气管扩张和寿命缩短。铜绿假单胞菌表达多种粘附素,包括已知结合上皮细胞的凝集素和粘蛋白糖缀合物。阻断碳水化合物介导的宿主-病原体和生物膜内相互作用对于定植的启动和持续至关重要,为抗感染治疗策略提供了希望。为了为抗粘连治疗提供信息,我们分析了来自 CF 和非 CF 来源的铜绿假单胞菌的单糖结合,并评估了特定的细菌表型特征是否影响碳水化合物结合模式。着眼于细胞水平,显微镜和荧光分光光度测量工具可以对铜绿假单胞菌与一组具有不同悬垂单糖的荧光糖聚合物的结合进行溶液相分析。所有铜绿假单胞菌都表现出与 α-D-半乳糖、β-DN-乙酰半乳糖胺和 β-D-半乳糖-3-硫酸盐特异性的糖聚合物的显着结合。在每种文化中,都有一小部分亚群负责结合。碳水化合物异头构型和硫酸酯的存在显着影响结合。虽然这种来自 CF 宿主的机会性病原体呈现出各种菌落形态和生理活性,但没有表型、生理或结构特征预测单糖结合的增强或减弱。对于抗粘连治疗策略很重要,这些发现表明,无论表型或临床来源如何,铜绿假单胞菌都维持着一个可能容易与特定单糖的特定构型相关的小亚群。该报告提供了对全细胞铜绿假单胞菌碳水化合物结合谱的见解,以及成功的 CF 抗粘附和/或抗毒力抗感染药物必须竞争的背景。
更新日期:2024-04-16
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