promotes its own survival via choline-binding protein CbpC-mediated degradation of ATG14.

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 that serves to promote intracellular survival.