Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Microbiol Mol Biol Rev. 2020 Nov 25;85(1). doi: 10.1128/MMBR.00062-20.
Bacteria often reside in multicellular communities, called biofilms, held together by an extracellular matrix. In many bacteria, the major proteinaceous component of the biofilm are amyloid fibers. Amyloids are highly stable and structured protein aggregates which were known mostly to be associated with neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases. In recent years, microbial amyloids were identified also in other species and shown to play major roles in microbial physiology and virulence. For example, amyloid fibers assemble on the bacterial cell surface as a part of the extracellular matrix and are extremely important to the scaffolding and structural integrity of biofilms, which contribute to microbial resilience and resistance. Furthermore, microbial amyloids play fundamental nonscaffold roles that contribute to the development of biofilms underlying numerous persistent infections. Here, we review several nonscaffold roles of bacterial amyloid proteins, including bridging cells during collective migration, acting as regulators of cell fate, as toxins against other bacteria or against host immune cells, and as modulators of the hosts' immune system. These overall points on the complexity of the amyloid fold in encoding numerous activities, which offer approaches for the development of a novel repertoire of antivirulence therapeutics.
细菌经常存在于由细胞外基质连接在一起的多细胞群落中,称为生物膜。在许多细菌中,生物膜的主要蛋白质成分是淀粉样纤维。淀粉样纤维是高度稳定和结构化的蛋白质聚集体,主要与神经退行性疾病(如阿尔茨海默病、帕金森病和亨廷顿病)有关。近年来,微生物淀粉样纤维也在其他物种中被发现,并被证明在微生物生理学和毒力方面发挥着重要作用。例如,淀粉样纤维作为细胞外基质的一部分组装在细菌细胞表面,对生物膜的支架和结构完整性极其重要,有助于微生物的弹性和抗性。此外,微生物淀粉样纤维发挥着基本的非支架作用,有助于多种持续感染下生物膜的形成。在这里,我们回顾了几种细菌淀粉样蛋白的非支架作用,包括在群体迁移过程中连接细胞、作为细胞命运的调节剂、作为针对其他细菌或宿主免疫细胞的毒素、以及作为宿主免疫系统的调节剂。这些关于淀粉样折叠在编码众多活性方面的复杂性的总体观点为开发新型抗病毒治疗方法提供了途径。