Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A Streptococcus
Group A streptococcus (GAS) is an important human pathogen that causes a wide variety of cutaneous and systemic infections. Although originally thought to be an extracellular bacterium, numerous studies have demonstrated that GAS can trigger internalization into nonimmune cells to escape from immune...
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American Society for Microbiology
2017-07-01
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doaj-98fb7c0eadc544c8854fdfd634f745622021-07-02T04:34:47ZengAmerican Society for MicrobiologymBio2150-75112017-07-0184e00899-1710.1128/mBio.00899-17Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A StreptococcusYi-Lin ChengYan-Wei WuChih-Feng KuoShiou-Ling LuFu-Tong LiuRobert AndersonChiou-Feng LinYi-Ling LiuWan-Yu WangYing-Da ChenPo-Xing ZhengJiunn-Jong WuYee-Shin LinJohn T. PattonGroup A streptococcus (GAS) is an important human pathogen that causes a wide variety of cutaneous and systemic infections. Although originally thought to be an extracellular bacterium, numerous studies have demonstrated that GAS can trigger internalization into nonimmune cells to escape from immune surveillance or antibiotic-mediated killing. Epithelial cells possess a defense mechanism involving autophagy-mediated targeting and killing of GAS within lysosome-fused autophagosomes. In endothelial cells, in contrast, we previously showed that autophagy is not sufficient for GAS killing. In the present study, we showed higher galectin-3 (Gal-3) expression and lower Gal-8 expression in endothelial cells than in epithelial cells. The recruitment of Gal-3 to GAS is higher and the recruitment of Gal-8 to GAS is lower in endothelial cells than in epithelial cells. We further showed that Gal-3 promotes GAS replication and diminishes the recruitment of Gal-8 and ubiquitin, the latter of which is a critical protein for autophagy sequestration. After knockdown of Gal-3 in endothelial cells, the colocalization of Gal-8, parkin, and ubiquitin-decorated GAS is significantly increased, as is the interaction of Gal-8 and parkin, an E3 ligase. Furthermore, inhibition of Gal-8 in epithelial cells attenuates recruitment of parkin; both Gal-8 and parkin contribute to ubiquitin recruitment and GAS elimination. Animal studies confirmed that Gal-3-knockout mice develop less-severe skin damage and that GAS replication can be detected only in the air pouch and not in organs and endothelial cells. These results demonstrate that Gal-3 inhibits ubiquitin recruitment by blocking Gal-8 and parkin recruitment, resulting in GAS replication in endothelial cells.http://mbio.asm.org/cgi/content/full/8/4/e00899-17 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yi-Lin Cheng Yan-Wei Wu Chih-Feng Kuo Shiou-Ling Lu Fu-Tong Liu Robert Anderson Chiou-Feng Lin Yi-Ling Liu Wan-Yu Wang Ying-Da Chen Po-Xing Zheng Jiunn-Jong Wu Yee-Shin Lin John T. Patton |
spellingShingle |
Yi-Lin Cheng Yan-Wei Wu Chih-Feng Kuo Shiou-Ling Lu Fu-Tong Liu Robert Anderson Chiou-Feng Lin Yi-Ling Liu Wan-Yu Wang Ying-Da Chen Po-Xing Zheng Jiunn-Jong Wu Yee-Shin Lin John T. Patton Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A Streptococcus mBio |
author_facet |
Yi-Lin Cheng Yan-Wei Wu Chih-Feng Kuo Shiou-Ling Lu Fu-Tong Liu Robert Anderson Chiou-Feng Lin Yi-Ling Liu Wan-Yu Wang Ying-Da Chen Po-Xing Zheng Jiunn-Jong Wu Yee-Shin Lin John T. Patton |
author_sort |
Yi-Lin Cheng |
title |
Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A Streptococcus |
title_short |
Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A Streptococcus |
title_full |
Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A Streptococcus |
title_fullStr |
Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A Streptococcus |
title_full_unstemmed |
Galectin-3 Inhibits Galectin-8/Parkin-Mediated Ubiquitination of Group A Streptococcus |
title_sort |
galectin-3 inhibits galectin-8/parkin-mediated ubiquitination of group a streptococcus |
publisher |
American Society for Microbiology |
series |
mBio |
issn |
2150-7511 |
publishDate |
2017-07-01 |
description |
Group A streptococcus (GAS) is an important human pathogen that causes a wide variety of cutaneous and systemic infections. Although originally thought to be an extracellular bacterium, numerous studies have demonstrated that GAS can trigger internalization into nonimmune cells to escape from immune surveillance or antibiotic-mediated killing. Epithelial cells possess a defense mechanism involving autophagy-mediated targeting and killing of GAS within lysosome-fused autophagosomes. In endothelial cells, in contrast, we previously showed that autophagy is not sufficient for GAS killing. In the present study, we showed higher galectin-3 (Gal-3) expression and lower Gal-8 expression in endothelial cells than in epithelial cells. The recruitment of Gal-3 to GAS is higher and the recruitment of Gal-8 to GAS is lower in endothelial cells than in epithelial cells. We further showed that Gal-3 promotes GAS replication and diminishes the recruitment of Gal-8 and ubiquitin, the latter of which is a critical protein for autophagy sequestration. After knockdown of Gal-3 in endothelial cells, the colocalization of Gal-8, parkin, and ubiquitin-decorated GAS is significantly increased, as is the interaction of Gal-8 and parkin, an E3 ligase. Furthermore, inhibition of Gal-8 in epithelial cells attenuates recruitment of parkin; both Gal-8 and parkin contribute to ubiquitin recruitment and GAS elimination. Animal studies confirmed that Gal-3-knockout mice develop less-severe skin damage and that GAS replication can be detected only in the air pouch and not in organs and endothelial cells. These results demonstrate that Gal-3 inhibits ubiquitin recruitment by blocking Gal-8 and parkin recruitment, resulting in GAS replication in endothelial cells. |
url |
http://mbio.asm.org/cgi/content/full/8/4/e00899-17 |
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