Pneumococcal cell surface-exposed choline-binding proteins (CBPs) play pivotal roles in multiple infectious processes with pneumococci. Intracellular pneumococci can be recognized at multiple steps during bactericidal autophagy. However, whether CBPs are involved in pneumococci-induced autophagic processes remains unknown. In this study, we demonstrate that CbpC from S. pneumoniae strain TIGR4 activates autophagy through an interaction with Atg14. However, S. pneumoniae also interferes with autophagy by deploying CbpC as a decoy to cause autophagic degradation of Atg14 through an interaction with p62/SQSTM1. Thus, S. pneumoniae suppresses the autophagic degradation of intracellular pneumococci and survives within cells. Domain analysis reveals that the coiled-coil domain of Atg14 and residue Y83 of the dp3 domain in the N-terminal region of CbpC are crucial for both the CbpC-Atg14 interaction and the subsequent autophagic degradation of Atg14. Although homology modeling indicates that CbpC orthologs have similar structures in the dp3 domain, autophagy induction through Atg14 binding is an intrinsic property of CbpC. Our data provide novel insights into the evolutionary hijacking of host-defense systems by intracellular pneumococci.

中文翻译：

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肺炎链球菌通过部署 CbpC 作为 Atg14 消耗的诱饵来劫持宿主自噬。

肺炎球菌细胞表面暴露的胆碱结合蛋白 (CBP) 在肺炎球菌的多种感染过程中起关键作用。在杀菌自噬过程中，可以在多个步骤中识别细胞内肺炎球菌。然而，CBPs 是否参与肺炎球菌诱导的自噬过程仍然未知。在这项研究中，我们证明来自肺炎链球菌 TIGR4 菌株的 CbpC 通过与 Atg14 的相互作用激活自噬。然而，肺炎链球菌也通过将 CbpC 作为诱饵来干扰自噬，通过与 p62/SQSTM1 的相互作用引起 Atg14 的自噬降解。因此，肺炎链球菌抑制细胞内肺炎球菌的自噬降解并在细胞内存活。结构域分析表明，Atg14 的卷曲螺旋结构域和 CbpC N 末端区域 dp3 结构域的残基 Y83 对于 CbpC-Atg14 相互作用和随后的 Atg14 自噬降解都至关重要。尽管同源性模型表明 CbpC 直系同源物在 dp3 结构域中具有相似的结构，但通过 Atg14 结合的自噬诱导是 CbpC 的固有特性。我们的数据为细胞内肺炎球菌对宿主防御系统的进化劫持提供了新的见解。