The Acinetobacter baumannii Autotransporter Adhesin Ata Recognizes Host Glycans as High-Affinity Receptors

Acinetobacter baumannii is a significant opportunistic pathogen responsible for infections of the lung, blood, skin, urinary tract, and soft tissues, with some strains exhibiting almost complete resistance to commonly used antibiotics. This multidrug resistance, together with a dearth of new antibiotic development, mean novel methods of treatment and prevention are urgently needed. Although many A. baumannii factors required to colonize the host have been identified, little is known about the specific host molecules recognized by these factors. A. baumannii produces a trimeric autotransporter adhesin known as Ata that has been previously demonstrated to bind components of the host cell’s extracellular matrix, which are often heavily glycosylated. We hypothesized that Ata would exhibit lectin activity which would play a role in adherence to the host cell surface. Our biophysical analysis using glycan arrays and surface plasmon resonance demonstrated that Ata binds galactose, N-acetylglucosamine, and galactose (β1–3/4) N-acetylglucosamine with high-affinity. These structures are present on many of the proteins which were previously reported to be bound by Ata. We also demonstrated that the recognition of human plasma fibronectin by Ata requires this ability to bind glycans, as the interaction between Ata and fibronectin does not occur when fibronectin is deglycosylated. This strongly suggests a key role for Ata lectin activity during host adherence. This information will assist in directing the development of new and effective treatments to block host interactions using glycans and/or novel compounds in multidrug resistant A. baumannii infections.

鲍曼不动杆菌（Acinetobacter baumannii）是一种重要的机会致病菌，可引发肺部、血液、皮肤、尿路及软组织感染，部分菌株对常用抗生素几乎完全耐药。这种多重耐药性叠加新型抗生素研发的匮乏，使得新型治疗与预防手段的开发迫在眉睫。尽管目前已鉴定出诸多鲍曼不动杆菌定植宿主所需的致病因子，但对于这些因子所识别的宿主特异性分子仍知之甚少。鲍曼不动杆菌可分泌一种名为Ata的三聚体自转运黏附素，既往研究已证实其能结合宿主细胞外基质的组分，而这些组分通常存在大量糖基化修饰。我们提出假说，认为Ata具备凝集素活性，该活性在宿主细胞黏附过程中发挥作用。通过糖芯片与表面等离子体共振（surface plasmon resonance, SPR）开展的生物物理分析显示，Ata可高亲和力结合半乳糖、N-乙酰葡糖胺，以及半乳糖（β1–3/4）N-乙酰葡糖胺。上述糖结构广泛存在于此前报道的Ata所结合的诸多蛋白中。我们还证实，Ata识别人体血浆纤连蛋白的过程依赖其糖结合能力：当纤连蛋白去糖基化后，Ata与纤连蛋白之间的相互作用便不复存在。这一结果强烈表明，Ata的凝集素活性在宿主黏附过程中发挥关键作用。本研究成果可为开发新型有效治疗手段提供指导，通过利用糖分子或新型化合物阻断多重耐药鲍曼不动杆菌的宿主相互作用过程，从而治疗相关感染。