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Emerging enterococcus pore-forming toxins with MHC/HLA-I as receptors.
Xiong, Xiaozhe; Tian, Songhai; Yang, Pan; Lebreton, Francois; Bao, Huan; Sheng, Kuanwei; Yin, Linxiang; Chen, Pengsheng; Zhang, Jie; Qi, Wanshu; Ruan, Jianbin; Wu, Hao; Chen, Hong; Breault, David T; Wu, Hao; Earl, Ashlee M; Gilmore, Michael S; Abraham, Jonathan; Dong, Min.
Affiliation
  • Xiong X; Department of Urology, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
  • Tian S; Department of Urology, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
  • Yang P; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
  • Lebreton F; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Multidrug-Resistant Organism Repository and Survei
  • Bao H; Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA.
  • Sheng K; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.
  • Yin L; Department of Urology, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
  • Chen P; Department of Urology, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
  • Zhang J; Department of Urology, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
  • Qi W; Division of Endocrinology, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Ruan J; Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Immunology, University of Connecticut Health School of Medicine, Farmington, CT 06030, USA.
  • Wu H; Vascular Biology Program, Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Chen H; Vascular Biology Program, Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Breault DT; Division of Endocrinology, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
  • Wu H; Program in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Earl AM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Gilmore MS; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: michael_gilmore@meei.harvard.e
  • Abraham J; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: jonathan_abraham@hms.harvard.edu.
  • Dong M; Department of Urology, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: min.dong@childrens.harvard.edu.
Cell ; 185(7): 1157-1171.e22, 2022 03 31.
Article in En | MEDLINE | ID: mdl-35259335
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 ß-barrel pore-forming toxins with a ß-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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bacterial Toxins / Leukocytes, Mononuclear / Enterococcus / Virulence Factors Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cell Year: 2022 Type: Article Affiliation country: United States
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bacterial Toxins / Leukocytes, Mononuclear / Enterococcus / Virulence Factors Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cell Year: 2022 Type: Article Affiliation country: United States