National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01NS080833
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01NS117626
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI132387
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI139087
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI158503
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R21NS106159
米国
引用
ジャーナル: Cell / 年: 2022 タイトル: Emerging enterococcus pore-forming toxins with MHC/HLA-I as receptors. 著者: Xiaozhe Xiong / Songhai Tian / Pan Yang / Francois Lebreton / Huan Bao / Kuanwei Sheng / Linxiang Yin / Pengsheng Chen / Jie Zhang / Wanshu Qi / Jianbin Ruan / Hao Wu / Hong Chen / David T ...著者: Xiaozhe Xiong / Songhai Tian / Pan Yang / Francois Lebreton / Huan Bao / Kuanwei Sheng / Linxiang Yin / Pengsheng Chen / Jie Zhang / Wanshu Qi / Jianbin Ruan / Hao Wu / Hong Chen / David T Breault / Hao Wu / Ashlee M Earl / Michael S Gilmore / Jonathan Abraham / Min Dong / 要旨: Enterococci are a part of human microbiota and a leading cause of multidrug resistant infections. Here, we identify a family of Enterococcus pore-forming toxins (Epxs) in E. faecalis, E. faecium, ...Enterococci are a part of human microbiota and a leading cause of multidrug resistant infections. Here, we identify a family of Enterococcus pore-forming toxins (Epxs) in E. faecalis, E. faecium, and E. hirae strains isolated across the globe. Structural studies reveal that Epxs form a branch of β-barrel pore-forming toxins with a β-barrel protrusion (designated the top domain) sitting atop the cap domain. Through a genome-wide CRISPR-Cas9 screen, we identify human leukocyte antigen class I (HLA-I) complex as a receptor for two members (Epx2 and Epx3), which preferentially recognize human HLA-I and homologous MHC-I of equine, bovine, and porcine, but not murine, origin. Interferon exposure, which stimulates MHC-I expression, sensitizes human cells and intestinal organoids to Epx2 and Epx3 toxicity. Co-culture with Epx2-harboring E. faecium damages human peripheral blood mononuclear cells and intestinal organoids, and this toxicity is neutralized by an Epx2 antibody, demonstrating the toxin-mediated virulence of Epx-carrying Enterococcus.