Endothelial cells are intrinsically defective in xenophagy of Streptococcus pyogenes

PLoS Pathogens

Tamotsu Yoshimori¹  Hiroko Omori²  Tsuyoshi Kawabata³  Tatsuya Kusaba³  Hirokazu Arimoto⁴  Ryo Iwamoto⁴  Shiou-Ling Lu⁴  Yi-Lin Cheng⁵  Yee-Shin Lin⁶  Takeshi Noda⁷  Maho Hamasaki⁸ 

[1]Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Osaka, Japan

[2]Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National-Yang Ming University, Taipei, Taiwan

[3]Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan

[4]Department of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan

[5]Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

[6]Graduate School of Frontier Bioscience, Osaka University, Osaka, Japan

[7]Graduate School of Life Sciences, Tohoku University, Sendai, Japan

[8]Research Institute for Microbial Disease, Osaka University, Osaka, Japan

关键词: Endothelial cells;    Autophagic cell death;    Epithelial cells;    Ubiquitination;    Nitric oxide;    Small interfering RNAs;    Salmonella;    Salmonellosis;   

DOI  :  10.1371/journal.ppat.1006444

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Group A Streptococcus (GAS) is deleterious pathogenic bacteria whose interaction with blood vessels leads to life-threatening bacteremia. Although xenophagy, a special form of autophagy, eliminates invading GAS in epithelial cells, we found that GAS could survive and multiply in endothelial cells. Endothelial cells were competent in starvation-induced autophagy, but failed to form double-membrane structures surrounding GAS, an essential step in xenophagy. This deficiency stemmed from reduced recruitment of ubiquitin and several core autophagy proteins in endothelial cells, as demonstrated by the fact that it could be rescued by exogenous coating of GAS with ubiquitin. The defect was associated with reduced NO-mediated ubiquitin signaling. Therefore, we propose that the lack of efficient clearance of GAS in endothelial cells is caused by their intrinsic inability to target GAS with ubiquitin to promote autophagosome biogenesis for xenophagy.

【 授权许可】

CC BY