title: Streptococcus pneumoniae induces autophagy through the inhibition of the PI3K-I/Akt/mTOR pathway and ROS hypergeneration in A549 cells.
abstract: The present study focused on the action mechanism of S. pneumoniae (Sp) in inducing autophagy in human alveolar epithelial cells. Sp, a gram-positive extracellular bacterium, activates autophagy with considerably increased microtuble-associated protein light chain 3 (LC3) punctation in A549 cells. The accumulation of typical autophagosomes and conjugation of LC3 to phosphatidylethanolamine were observed in Sp-infected cells as an indication of autophagy. Using the pneumolysin (PLY) mutant, we successfully demonstrated that PLY is involved in initiating autophagy without affecting the expression levels of PI3K-III and Beclin1. PLY-mediated autophagy depends on the inhibition of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Furthermore, Sp could also lead to the reactive oxygen species (ROS) hypergeneration in A549 cells. Taken together, Sp infection-induced autophagy is PLY-mediated through ROS hypergeneration and mTOR inhibition. PI3K-I and rapamycin (autophagy inducers) enhanced bacterial clearance, whereas wortmannin (autophagy inhibitor) and acetylcysteine (ROS inhibitor) reduced intracellular bacteria clearance. Thus, Sp-induced autophagy represents a host-protective mechanism, providing new insight into the pathogenesis of respiratory tract Sp infection.
authors: Department of Laboratory medicine, the Second Hospital Affiliated to Chongqing Medical University, Chongqing, China.
authors: Pu
authors: P
authors: Li
authors: Department of Laboratory medicine, the First Hospital Affiliated to Chongqing Medical University, Chongqing, China.
authors: Jing
authors: J
authors: Shi
authors: Department of Laboratory medicine, the Second Hospital Affiliated to Chongqing Medical University, Chongqing, China.
authors: Qiao
authors: Q
authors: He
authors: Department of Laboratory medicine, the Second Hospital Affiliated to Chongqing Medical University, Chongqing, China.
authors: Qin
authors: Q
authors: Hu
authors: Department of Laboratory medicine, the Second Hospital Affiliated to Chongqing Medical University, Chongqing, China.
authors: Yun Ying
authors: YY
authors: Wang
authors: Department of Laboratory medicine, the Second Hospital Affiliated to Chongqing Medical University, Chongqing, China.
authors: Li Jun
authors: LJ
authors: Zhang
authors: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, Madrid, Spain.
authors: Wai Ting
authors: WT
authors: Chan
authors: Department of Laboratory medicine, the Second Hospital Affiliated to Chongqing Medical University, Chongqing, China.
authors: Wei-Xian
authors: WX
authors: Chen
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000704:Analysis of Variance; D000730:Androstadienes / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics; D000071186:Beclin-1; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011650:Pulmonary Alveoli / Q000166:cytology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity / Q000502:physiology*; D013301:Streptolysins / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000111:Acetylcysteine; D000730:Androstadienes; D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D000071186:Beclin-1; D017931:DNA Primers; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D017382:Reactive Oxygen Species; D013301:Streptolysins; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin; C491997:BECN1 protein, human; C477012:MAP1LC3A protein, human; C032290:plY protein, Streptococcus pneumoniae; C546842:MTOR protein, human