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TitleEmerging enterococcus pore-forming toxins with MHC/HLA-I as receptors.
Journal, issue, pagesCell, Vol. 185, Issue 7, Page 1157-1171.e22, Year 2022
Publish dateMar 31, 2022
AuthorsXiaozhe 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 /
PubMed AbstractEnterococci 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.
External linksCell / PubMed:35259335 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.87 - 3 Å
Structure data

25673

7t4e

EMDB-25673, PDB-7t4e:
Prepore structure of pore-forming toxin Epx1
Method: EM (single particle) / Resolution: 2.87 Å

PDB-7t4d:
Pore structure of pore-forming toxin Epx4
Method: X-RAY DIFFRACTION / Resolution: 3.0 Å

Chemicals

ChemComp-MPD:
(4S)-2-METHYL-2,4-PENTANEDIOL / precipitant*YM / 2-Methyl-2,4-pentanediol

Source
  • enterococcus faecalis (bacteria)
  • enterococcus (bacteria)
KeywordsTOXIN / pore-forming toxin

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