Department of Immunology and Institute for Cellular and Molecular Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
Department of Haematology, Faculty of Health Sciences, University of Pretoria and Tshwane Academic Division of the National Health Laboratory Service, Pretoria 0001, South Africa.
Int J Mol Sci. 2018 Apr 11;19(4):1147. doi: 10.3390/ijms19041147.
Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, β-barrel pore-forming cytolysins, is the major protein virulence factor of the dangerous respiratory pathogen, (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired pneumonia (CAP), promoting colonization and invasion of the upper and lower respiratory tracts respectively, as well as extra-pulmonary dissemination of the pneumococcus. Notwithstanding its role in causing acute lung injury in severe CAP, PLY has also been implicated in the development of potentially fatal acute and delayed-onset cardiovascular events, which are now recognized as being fairly common complications of this condition. This review is focused firstly on updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial damage, specifically the direct cardiotoxic and immunosuppressive activities, as well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin. Secondly, on PLY-targeted therapeutic strategies including, among others, macrolide antibiotics, natural product antagonists, cholesterol-containing liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based preventive strategies. These sections are preceded by overviews of CAP in general, the role of the pneumococcus as the causative pathogen, the occurrence and types of CAP-associated cardiac complication, and the structure and biological activities of PLY.
肺炎球菌溶血素（PLY）是一种革兰氏阳性细菌、胆固醇依赖性、β-桶状孔形成细胞毒素家族的成员，是危险的呼吸道病原体肺炎球菌的主要蛋白毒力因子。PLY 在社区获得性肺炎（CAP）的发病机制中起着重要作用，分别促进上呼吸道和下呼吸道的定植和侵袭，以及肺炎球菌的肺外传播。尽管它在严重 CAP 引起急性肺损伤中起作用，但 PLY 也与潜在致命的急性和迟发性心血管事件的发展有关，这些事件现在被认为是这种疾病相当常见的并发症。这篇综述首先集中于更新 PLY 介导的心肌损伤的免疫发病机制中涉及的机制，特别是毒素的直接心脏毒性和免疫抑制活性，以及间接的促炎/促血栓形成活性。其次，介绍了针对 PLY 的治疗策略，包括大环内酯类抗生素、天然产物拮抗剂、含胆固醇的脂质体和全人源化单克隆抗体，以及基于疫苗的预防策略。这些部分之前是对 CAP 的概述、肺炎球菌作为病原体的作用、CAP 相关心脏并发症的发生和类型，以及 PLY 的结构和生物学活性。
