Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Hefei National Laboratory for Physical Sciences at Microscale, Laboratory of Structural Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Life Sciences and Medicine, School of Basic Medical Sciences, University of Science and Technology of China, Hefei 230027, China.
Toxins (Basel). 2021 Feb 9;13(2):128. doi: 10.3390/toxins13020128.
With the rapid growth of antibiotic-resistant bacteria, it is urgent to develop alternative therapeutic strategies. Pore-forming toxins (PFTs) belong to the largest family of virulence factors of many pathogenic bacteria and constitute the most characterized classes of pore-forming proteins (PFPs). Recent studies revealed the structural basis of several PFTs, both as soluble monomers, and transmembrane oligomers. Upon interacting with host cells, the soluble monomer of bacterial PFTs assembles into transmembrane oligomeric complexes that insert into membranes and affect target cell-membrane permeability, leading to diverse cellular responses and outcomes. Herein we have reviewed the structural basis of pore formation and interaction of PFTs with the host cell membrane, which could add valuable contributions in comprehensive understanding of PFTs and searching for novel therapeutic strategies targeting PFTs and interaction with host receptors in the fight of bacterial antibiotic-resistance.
随着抗生素耐药菌的迅速增长，开发替代治疗策略迫在眉睫。成孔毒素 (PFT) 属于许多致病菌毒力因子中最大的家族，构成了最具特征性的孔形成蛋白 (PFP) 类别。最近的研究揭示了几种 PFT 的结构基础，包括可溶性单体和跨膜寡聚体。与宿主细胞相互作用时，细菌 PFT 的可溶性单体组装成跨膜寡聚体复合物，插入到膜中并影响靶细胞的膜通透性，导致多种细胞反应和结果。本文综述了 PFT 成孔和与宿主细胞膜相互作用的结构基础，这可能有助于全面了解 PFT 及其针对 PFT 的新型治疗策略，并在对抗细菌抗生素耐药性方面寻找针对 PFT 与宿主受体相互作用的新策略。
