Multiple autophagic processes are triggered in response to bacterial infection as the host attempts to eliminate intracellular invaders. However, it is still unclear how the mechanisms contributing to canonical macroautophagy/autophagy, including xenophagy, coordinate with the more recently described features that are characteristic of noncanonical autophagy. Recently, we revealed that infection with Streptococcus pneumoniae can trigger the formation of RB1CC1/FIP200-independent LC3-associated phagosome-like vacuoles (PcLVs) that contain the pneumococci at an early stage of infection. We also found that interactions of SQSTM1/p62 with the ATG16L1 WD domain are essential for PcLV formation. Intriguingly, PcLVs were required for the subsequent generation of bactericidal autophagic vacuoles (PcAVs). Furthermore, we also identified LC3-delocalized SQSTM1-positive PcLVs as intracellular intermediates that link PcLVs and PcAVs. These findings reveal a novel multi-step mechanism that contributes to xenophagy of the critical S. pneumoniae respiratory pathogen.

中文翻译：

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感染早期非靶向自噬靶向肺炎链球菌的多步机制和生物学作用。

当宿主试图消除细胞内入侵者时，响应细菌感染而触发了多个自噬过程。但是，尚不清楚促成规范的宏观自噬/自噬的机制（包括异种吞噬）如何与最近描述的非规范自噬的特征协调。最近，我们发现，肺炎链球菌感染可在感染早期触发包含肺炎球菌的RB1CC1 / FIP200独立的LC3相关吞噬体样液泡（PcLV）的形成。我们还发现，SQSTM1 / p62与ATG16L1 WD域的相互作用对于PcLV的形成至关重要。有趣的是，随后的杀菌自噬泡（PcAVs）的产生需要PcLV。此外，我们还确定了LC3脱SQSTM1阳性PcLVs为连接PcLVs和PcAVs的细胞内中间体。这些发现揭示了一种新的多步机制，该机制有助于关键性肺炎链球菌呼吸道病原体的异种吞噬。