biostudies-literatureXiong XNICHD NIH HHSNIBIB NIH HHSNCRR NIH HHSNIDDK NIH HHSNIAID NIH HHSNHLBI NIH HHSNINDS NIH HHSNIGMS NIH HHS1157-1171.e22https://www.ebi.ac.uk/biostudies/studies/S-EPMC8978092biostudies-literatureUnknown185(7)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 CellEmerging enterococcus pore-forming toxins with MHC/HLA-I as receptors.PMC8978092R01 HL093242R01 AI158503P30 GM124165R01 HL130845P01 AI083214R01 AI132387R01 HL137229R01 EB021908T32 HL007917R01 AI139087P30 HD018655R01 NS080833R21 NS106159HHSN272200900018CP30 DK034854R01 HL156362R01 NS117626S10 RR029205DP2 GM140920U19 AI110818Chen PZhang JDong MQi WAbraham JLebreton FChen HXiong XWu HRuan JGilmore MSSheng KBreault DTBao HYang PTian SEarl AMYin LfalseEmerging enterococcus pore-forming toxins with MHC/HLA-I as receptors.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 2022-01-01T00:00:00Z2022 Mar2025-04-19T13:32:28.552Z2024-11-15T19:24:42.351ZS-EPMC89780923525933510.1016/j.cell.2022.02.002