Content area
Full text
About the Authors:
Shiou-Ling Lu
Affiliation: Department of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
Tsuyoshi Kawabata
Affiliation: Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan
Yi-Lin Cheng
Affiliations Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National-Yang Ming University, Taipei, Taiwan
Hiroko Omori
Affiliation: Research Institute for Microbial Disease, Osaka University, Osaka, Japan
Maho Hamasaki
Affiliation: Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan
Tatsuya Kusaba
Affiliation: Department of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
Ryo Iwamoto
Affiliation: Department of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
Hirokazu Arimoto
Affiliation: Graduate School of Life Sciences, Tohoku University, Sendai, Japan
ORCID http://orcid.org/0000-0002-0086-6117
Takeshi Noda
Affiliations Graduate School of Frontier Bioscience, Osaka University, Osaka, Japan, Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Osaka, Japan
ORCID http://orcid.org/0000-0003-3581-7961
Yee-Shin Lin
Affiliations Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan
Tamotsu Yoshimori
* E-mail: [email protected]
Affiliations Department of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan, Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan
ORCID http://orcid.org/0000-0001-9787-3788Abstract
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.
Author summary
Autophagy is an intracellular bulk...