Streptococcus pneumoniae

is an opportunistic bacterial pathogen that can promote severe infection by overcoming the epithelial and blood-brain barrier. Pneumococcal cell-surface virulence factors, including cell wall-anchored choline-binding proteins (Cbps) play pivotal roles in promoting invasive disease. We reported previously that intracellular pneumococci were detected by hierarchical macroautophagic/autophagic processes that ultimately lead to bacterial elimination. However, whether intracellular pneumococci can evade autophagy by deploying Cbps remains unclear. In this study, we explore the biological functions of Cbps and reveal their roles in manipulating the autophagic process. Specifically, we found that CbpC-activated autophagy takes place via its interactions with ATG14 (autophagy related 14) and SQSTM1/p62 (sequestosome1). Importantly, CbpC dampens host autophagy by promoting ATG14 degradation via the ATG14-CbpC-SQSTM1/p62 axis. CbpC-induced reductions in ATG14 levels result in impaired ATG14-STX17 complex formation. In pneumococcal-infected cells, ATG14 levels are dramatically reduced in a CbpC-dependent manner that results in suppression of autophagy-mediated degradation and enhanced bacterial survival. Taken together, our results reveal a novel mechanism via which pneumococci can manipulate host autophagy responses, in this case, by employing CbpC as a trap to promote ATG14 depletion. Our findings highlight a novel and sophisticated tactic used by S. pneumoniae that serves to promote intracellular survival.

中文翻译：

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肺炎链球菌通过胆碱结合蛋白CbpC介导的ATG14降解来促进自身生存。

肺炎链球菌

是机会性细菌病原体，可通过克服上皮和血脑屏障来促进严重感染。肺炎球菌的细胞表面毒力因子，包括细胞壁锚定的胆碱结合蛋白（Cbps），在促进浸润性疾病中起关键作用。我们以前报道过，细胞内肺炎球菌是通过分级的巨自噬/自噬过程检测到的，最终导致细菌清除。然而，尚不清楚细胞内肺炎球菌是否可以通过部署Cbps逃避自噬。在这项研究中，我们探讨了Cbps的生物学功能，并揭示了它们在操纵自噬过程中的作用。具体而言，我们发现CbpC激活的自噬通过其与ATG14（自噬相关的14）和SQSTM1 / p62（sequestosome1）的相互作用而发生。重要的，CbpC通过促进ATG14-CbpC-SQSTM1 / p62轴促进ATG14降解来抑制宿主自噬。CbpC诱导的ATG14水平降低导致ATG14-STX17复合物形成受损。在肺炎球菌感染的细胞中，ATG14水平以CbpC依赖性方式显着降低，从而导致自噬介导的降解受到抑制，细菌存活率提高。两者合计，我们的结果揭示了一种新的机制，通过这种机制，肺炎球菌可以利用CbpC作为诱捕剂来促进ATG14耗竭，从而操纵宿主自噬反应。我们的发现强调了 ATG14水平以CbpC依赖性的方式显着降低，从而导致自噬介导的降解受到抑制，细菌存活率提高。两者合计，我们的结果揭示了一种新的机制，通过这种机制，肺炎球菌可以利用CbpC作为诱捕剂来促进ATG14耗竭，从而操纵宿主自噬反应。我们的发现强调了 ATG14水平以CbpC依赖性的方式显着降低，从而导致自噬介导的降解受到抑制，细菌存活率提高。两者合计，我们的结果揭示了一种新的机制，通过这种机制，肺炎球菌可以利用CbpC作为诱捕剂来促进ATG14耗竭，从而操纵宿主自噬反应。我们的发现强调了肺炎链球菌可促进细胞内存活。