Joint Biotechnology Laboratory, MediCity, Faculty of Medicine, University of Turku, Turku, Finland.
Department of Physics, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden.
Nature. 2022 Sep;609(7926):335-340. doi: 10.1038/s41586-022-05095-0. Epub 2022 Jul 19.
Adhesive pili assembled through the chaperone-usher pathway are hair-like appendages that mediate host tissue colonization and biofilm formation of Gram-negative bacteria. Archaic chaperone-usher pathway pili, the most diverse and widespread chaperone-usher pathway adhesins, are promising vaccine and drug targets owing to their prevalence in the most troublesome multidrug-resistant pathogens. However, their architecture and assembly-secretion process remain unknown. Here, we present the cryo-electron microscopy structure of the prototypical archaic Csu pilus that mediates biofilm formation of Acinetobacter baumannii-a notorious multidrug-resistant nosocomial pathogen. In contrast to the thick helical tubes of the classical type 1 and P pili, archaic pili assemble into an ultrathin zigzag architecture secured by an elegant clinch mechanism. The molecular clinch provides the pilus with high mechanical stability as well as superelasticity, a property observed for the first time, to our knowledge, in biomolecules, while enabling a more economical and faster pilus production. Furthermore, we demonstrate that clinch formation at the cell surface drives pilus secretion through the outer membrane. These findings suggest that clinch-formation inhibitors might represent a new strategy to fight multidrug-resistant bacterial infections.
黏附菌毛通过伴侣蛋白- usher 途径组装，是介导革兰氏阴性菌宿主组织定植和生物膜形成的毛发状附属物。古老的伴侣蛋白- usher 途径菌毛是最具多样性和广泛分布的伴侣蛋白- usher 途径黏附素，由于它们在最令人头疼的多药耐药病原体中普遍存在，因此是有前途的疫苗和药物靶点。然而，它们的结构和组装-分泌过程仍然未知。在这里，我们展示了介导鲍曼不动杆菌生物膜形成的原型古老 Csu 菌毛的冷冻电镜结构，鲍曼不动杆菌是一种臭名昭著的多药耐药医院获得性病原体。与经典的 1 型和 P 菌毛的厚螺旋管不同，古老的菌毛组装成一种超精细的锯齿状结构，由一个优雅的扣合机制固定。分子扣合赋予菌毛高度的机械稳定性和超弹性，据我们所知，这是生物分子中首次观察到的特性，同时使菌毛的生产更经济、更快。此外，我们证明了在细胞表面形成的扣合驱动菌毛通过外膜分泌。这些发现表明，扣合形成抑制剂可能代表一种对抗多药耐药细菌感染的新策略。
