Trimeric Autotransporter Adhesins (TAA) found in Gram-negative bacteria play a key role in virulence. This is the case of Burkholderia cepacia complex (Bcc), a group of related bacteria able to cause infections in patients with cystic fibrosis. These bacteria use TAAs, among other virulence factors, to bind to host protein receptors and their carbohydrate ligands. Blocking such contacts is an attractive approach to inhibit Bcc infections. In this study, using an antibody produced against the TAA BCAM2418 from the epidemic strain Burkholderia cenocepacia K56-2, we were able to uncover its roles as an adhesin and the type of host glycan structures that serve as recognition targets. The neutralisation of BCAM2418 was found to cause a reduction in the adhesion of the bacteria to bronchial cells and mucins. Moreover, in vivo studies have shown that the anti-BCAM2418 antibody exerted an inhibitory effect during infection in Galleria mellonella. Finally, inferred by glycan arrays, we were able to predict for the first time, host glycan epitopes for a TAA. We show that BCAM2418 favoured binding to 3′sialyl-3-fucosyllactose, histo-blood group A, α-(1,2)-linked Fuc-containing structures, Lewis structures and GM1 gangliosides. In addition, the glycan microarrays demonstrated similar specificities of Burkholderia species for their most intensely binding carbohydrates.

中文翻译：

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新洋葱伯克霍尔德菌 BCAM2418 诱导的抗体可抑制细菌粘附，为感染提供保护，并能够将宿主聚糖鉴定为粘附素靶标

在革兰氏阴性菌中发现的三聚体自转运体粘附素 (TAA) 在毒力中起关键作用。洋葱伯克霍尔德菌复合体 (Bcc)就是这种情况，这是一组能够引起囊性纤维化患者感染的相关细菌。这些细菌使用 TAA 以及其他毒力因子与宿主蛋白质受体及其碳水化合物配体结合。阻止此类接触是抑制 Bcc 感染的一种有吸引力的方法。在这项研究中，使用一种针对来自流行菌株新洋葱伯克霍尔德氏菌的 TAA BCAM2418 产生的抗体K56-2，我们能够揭示它作为粘附素的作用以及作为识别目标的宿主聚糖结构的类型。发现 BCAM2418 的中和导致细菌对支气管细胞和粘蛋白的粘附减少。此外，体内研究表明，抗 BCAM2418 抗体在mellonella感染期间发挥抑制作用。最后，通过聚糖阵列推断，我们首次能够预测 TAA 的宿主聚糖表位。我们表明 BCAM2418 有利于与 3'sialyl-3-fucosyllactose、组织血型 A、α-(1,2)-连接的含 Fuc 结构、Lewis 结构和 GM1 神经节苷脂结合。此外，聚糖微阵列表现出与伯克霍尔德菌相似的特异性物种因为它们结合最强烈的碳水化合物。