Endothelial cells are intrinsically defective in xenophagy of Streptococcus pyogenes

Journal PLoS Pathog (2017)
Title Endothelial cells are intrinsically defective in xenophagy of Streptococcus pyogenes
Laboratory Laboratory of Intracellular Membrane Dynamics

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.


Lu SL (1), Kawabata T (2), Cheng YL (3, 4), Omori H (5), Hamasaki M (2), Kusaba T (1), Iwamoto R (1), Arimoto H (6), Noda T (7, 8), Lin YS (3, 9), Yoshimori T (1, 2)

  1. Department of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
  2. Department of Genetics, Graduate School of Medicine, Osaka University, Osaka, Japan.
  3. Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  4. Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National-Yang Ming University, Taipei, Taiwan.
  5. Research Institute for Microbial Disease, Osaka University, Osaka, Japan.
  6. Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
  7. Graduate School of Frontier Bioscience, Osaka University, Osaka, Japan.
  8. Center for Frontier Oral Science, Graduate School of Dentistry, Osaka University, Osaka, Japan.
  9. Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
PubMed 28683091