Escuela Superior de Ingeniería y Tecnología (ESIT), Universidad Internacional de La Rioja, UNIR, Logroño, La Rioja, Spain.
Genética, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.
PLoS One. 2023 Mar 22;18(3):e0282970. doi: 10.1371/journal.pone.0282970. eCollection 2023.
This systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction.
The databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework.
Forty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability.
Most of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis.
A panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.
本系统评价评估了肺炎球菌溶血素（PLY）作为治疗肺炎球菌感染的新疗法的靶点。肺炎球菌溶血素是所有类型肺炎球菌产生的主要毒力因子之一。这种毒素（53 kDa）是一种高度保守的蛋白质，与真核细胞中的胆固醇结合，形成导致细胞破坏的孔。
检索的数据库包括 MEDLINE、Web of Science 和 Scopus。研究人员通过标题、摘要和全文独立筛选文章，并通过达成共识解决出现的任何分歧。排除了其他语言（非英语）的文章、专利、病例报告、注释、章节书籍和综述。搜索限制在 2000 年至 2021 年。使用 OHAT 框架评估方法学质量。
综述了 41 篇描述不同抑制 PLY 分子作用的文章。简要地说，发现的抑制分子分为三组：通过结合和/或阻断 PLY 直接发挥作用的分子、通过阻止其对宿主细胞的作用间接发挥作用的分子，以及其机制未知的分子。尽管许多分子被提出作为毒素阻断剂，但只有少数分子，如抗生素、肽、固醇和他汀类药物，有可能作为临床治疗方法实施。相比之下，对于其他分子，只有少数研究在具有足够可靠性的动物模型中证明了其疗效。
大多数综述研究具有较高的置信水平。然而，本系统评价的一个局限性是研究缺乏同质性，这使得无法对结果进行统计比较或荟萃分析。
一组阻断 PLY 活性的分子与改善由肺炎球菌感染引发的炎症过程有关。一些分子已经用于治疗其他疾病，因此对肺炎球菌感染患者可能是安全的。这些患者可能受益于在感染初期进行二线治疗，以预防急性呼吸窘迫综合征和侵袭性肺炎球菌病。使用本文提出的化合物集进行进一步研究可能会进一步改善这些患者的临床管理。
