期刊
CELL REPORTS
卷 35, 期 11, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.109267
关键词
-
类别
资金
- National Institutes of Health (NIH) Immunologic Diseases and Basic Immunology [5T32AI007051-38]
- J. Craig Venter Institute
- NIH [AI118805, AI156898, AI146149, AI148368, AI114800]
- AHA [16GRNT30230007]
The study demonstrates the adhesion function of PspA to dying host cells and its importance in pneumococcal pneumonia, particularly in the context of co-infection with IAV. The binding of PspA to GAPDH protein is mediated through its specific alpha-helical domain, and a specific interaction between PspA and dying cells is identified.
Streptococcus pneumoniae (Spn) alone and during co-infection with influenza A virus (IAV) can result in severe pneumonia with mortality. Pneumococcal surface protein A (PspA) is an established virulence factor required for Spn evasion of lactoferricin and C-reactive protein-activated complement-mediated killing. Herein, we show that PspA functions as an adhesin to dying host cells. We demonstrate that PspA binds to host-derived glyceraldehyde-3-phosphate dehydrogenase (GAPDH) bound to outward-flipped phosphatidylserine residues on dying host cells. PspA-mediated adhesion was to apoptotic, pyroptotic, and necroptotic cells, but not healthy lung cells. Using isogenic mutants of Spn, we show that PspA-GAPDH-mediated binding to lung cells increases pneumococcal localization in the lower airway, and this is enhanced as a result of pneumolysin exposure or co-infection with IAV. PspA-mediated binding to GAPDH requires amino acids 230-281 in its alpha-helical domain with intratracheal inoculation of this PspA fragment alongside the bacteria reducing disease severity in an IAV/Spn pneumonia model.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据