| Literature DB >> 35259335 |
Xiaozhe Xiong1, Songhai Tian1, Pan Yang2, Francois Lebreton3, Huan Bao4, Kuanwei Sheng5, Linxiang Yin1, Pengsheng Chen1, Jie Zhang6, Wanshu Qi7, Jianbin Ruan8, Hao Wu11, Hong Chen9, David T Breault10, Hao Wu11, Ashlee M Earl12, Michael S Gilmore13, Jonathan Abraham14, Min Dong15.
Abstract
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.Entities:
Keywords: CRISPR screen; E. faecalis; E. faecium; E. hirae; Enterococcus; HLA-I; MHC-I; bacterial toxin; interferon; pore-forming toxin
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Year: 2022 PMID： 35259335 PMCID： PMC8978092 DOI： 10.1016/j.cell.2022.02.002
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850