Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology , Jena, Germany.
Centre for Electron Microscopy, Jena University Hospital, Friedrich-Schiller-University of Jena , Jena, Germany.
Infect Immun. 2023 Sep 14;91(9):e0015423. doi: 10.1128/iai.00154-23. Epub 2023 Aug 8.
is a Gram-positive opportunistic pathogen that can colonize the upper respiratory tract. It is a leading cause of a wide range of infectious diseases, including community-acquired pneumonia and meningitis. Pneumococcal infections cause 1-2 million deaths per year, most of which occur in developing countries. Here, we focused on three choline-binding proteins (CBPs), i.e., PspC, PspA, and LytA. These pneumococcal proteins have different surface-exposed regions but share related choline-binding anchors. These surface-exposed pneumococcal proteins are in direct contact with host cells and have diverse functions. We explored the role of the three CBPs on adhesion and pathogenicity in a human host by performing relevant imaging and functional analyses, such as electron microscopy, confocal laser scanning microscopy, and functional quantitative assays, targeting biofilm formation and the hemolytic capacity of . biofilm formation assays and electron microscopy experiments were used to examine the ability of knockout mutant strains lacking the lytA, pspC, or pspA genes to adhere to surfaces. We found that LytA plays an important role in robust synthesis of the biofilm matrix. PspA and PspC appeared crucial for the hemolytic effects of on human red blood cells. Furthermore, all knockout mutants caused less damage to endothelial cells than wild-type bacteria, highlighting the significance of each CPB for the overall pathogenicity of . Hence, in addition to their structural function within the cell wall of , each of these three surface-exposed CBPs controls or mediates multiple steps during bacterial pathogenesis.
是一种革兰氏阳性机会性病原体，可以定植在上呼吸道。它是多种传染病的主要病因，包括社区获得性肺炎和脑膜炎。肺炎球菌感染每年导致 100 万至 200 万人死亡，其中大多数发生在发展中国家。在这里，我们重点关注三种胆堿结合蛋白（CBPs），即 PspC、PspA 和 LytA。这些肺炎球菌蛋白具有不同的表面暴露区域，但具有相关的胆堿结合锚。这些表面暴露的肺炎球菌蛋白与宿主细胞直接接触，具有多种功能。我们通过进行相关的成像和功能分析，如电子显微镜、共聚焦激光扫描显微镜和功能定量分析，来探索这三种 CBPs 在人类宿主中的粘附和致病性作用，以研究生物膜形成和溶血能力。生物膜形成分析和电子显微镜实验用于检测缺乏 lytA、pspC 或 pspA 基因的敲除突变株粘附表面的能力。我们发现 LytA 在生物膜基质的强大合成中发挥重要作用。PspA 和 PspC 似乎对肺炎球菌对人红细胞的溶血作用至关重要。此外，所有敲除突变体对内皮细胞的损伤均小于野生型细菌，这突出了每个 CPB 对细菌整体致病性的重要性。因此，除了它们在细胞壁内的结构功能外，这三种表面暴露的 CBPs 中的每一种都控制或介导细菌发病机制中的多个步骤。
