Poster Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Roles of Gal-3 and Gal-8 in Group A streptococcus infection (#195)

Yi-Lin Cheng 1 2 , Jiunn Jong Wu 2 , Yee-Shin Lin 1
  1. Department of Microbiology and Immunology, National Cheng Kung University, Tainan, Taiwan
  2. Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan

Group A streptococcus (GAS) is an important human pathogen that causes a wide variety of cutaneous and systemic infections resulting in considerable morbidity and mortality worldwide. 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 the invading 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 show differential galectin (Gal)-3 and Gal-8 expression in endothelial cells and epithelial cells. The recruitment of Gal-3 to GAS is higher and the recruitment of Gal-8 to GAS is lower in endothelial cells compared to epithelial cells. We further show 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 and ubiquitin-decorated GAS is significantly increased. Animal studies confirmed that Gal-3-knockout mice develop less severe skin damage, and GAS replication can only be detected in the air pouch but not in organs and endothelial cells. These results demonstrate that Gal-3 inhibits ubiquitin recruitment by blocking Gal-8 resulting in GAS replication in endothelial cells.