Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, United States.
Front Cell Infect Microbiol. 2022 Feb 2;12:826264. doi: 10.3389/fcimb.2022.826264. eCollection 2022.
(), or the pneumococcus, is a Gram-positive bacterium that colonizes the upper airway. is an opportunistic pathogen capable of life-threatening disease should it become established in the lungs, gain access to the bloodstream, or disseminate to vital organs including the central nervous system. is encapsulated, allowing it to avoid phagocytosis, and current preventative measures against infection include polyvalent vaccines composed of capsular polysaccharide corresponding to its most prevalent serotypes. The pneumococcus also has a plethora of surface components that allow the bacteria to adhere to host cells, facilitate the evasion of the immune system, and obtain vital nutrients; one family of these are the choline-binding proteins (CBPs). Pneumococcal surface protein A (PspA) is one of the most abundant CBPs and confers protection against the host by inhibiting recognition by C-reactive protein and neutralizing the antimicrobial peptide lactoferricin. Recently our group has identified two new roles for PspA: binding to dying host cells via host-cell bound glyceraldehyde 3-phosphate dehydrogenase and co-opting of host lactate dehydrogenase to enhance lactate availability. These properties have been shown to influence localization and enhance virulence in the lower airway, respectively. Herein, we review the impact of CBPs, and in particular PspA, on pneumococcal pathogenesis. We discuss the potential and limitations of using PspA as a conserved vaccine antigen in a conjugate vaccine formulation. PspA is a vital component of the pneumococcal virulence arsenal - therefore, understanding the molecular aspects of this protein is essential in understanding pneumococcal pathogenesis and utilizing PspA as a target for treating or preventing pneumococcal pneumonia.
（肺炎链球菌），也称为肺炎球菌，是一种定植在上呼吸道的革兰氏阳性细菌。它是一种机会性病原体，如果在肺部定殖、进入血液、或传播到包括中枢神经系统在内的重要器官，它可能导致危及生命的疾病。肺炎链球菌被囊包围，使其能够逃避吞噬作用，目前预防感染的措施包括含有与其最常见血清型相对应荚膜多糖的多价疫苗。肺炎链球菌还有许多表面成分，使细菌能够黏附宿主细胞、逃避免疫系统，并获取重要营养物质；其中一类是胆碱结合蛋白（CBPs）。肺炎球菌表面蛋白 A（PspA）是最丰富的 CBPs 之一，通过抑制 C 反应蛋白的识别和中和抗菌肽乳铁蛋白，为宿主提供保护。最近，我们小组发现了 PspA 的两个新功能：通过与宿主细胞结合的甘油醛 3-磷酸脱氢酶结合，与死亡的宿主细胞结合，并利用宿主乳酸脱氢酶增强乳酸的可用性。这些特性分别被证明会影响细菌的定位并增强其在下呼吸道的毒力。本文综述了 CBPs，特别是 PspA，对肺炎链球菌发病机制的影响。我们讨论了将 PspA 作为一种保守的疫苗抗原用于缀合疫苗制剂的潜力和局限性。PspA 是肺炎链球菌毒力武器库的重要组成部分-因此，了解该蛋白的分子方面对于理解肺炎链球菌发病机制以及将 PspA 作为治疗或预防肺炎链球菌性肺炎的靶点至关重要。
