Evidence map›Paper›PMID 35259335›Full record

ArticleCell2022

Emerging enterococcus pore-forming toxins with MHC/HLA-I as receptors.

Xiaozhe Xiong, Songhai Tian, Pan Yang, Francois Lebreton, Huan Bao, Kuanwei Sheng, Linxiang Yin, Pengsheng Chen, Jie Zhang, Wanshu Qi and 9 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 2 pooled it
5.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Article
  7. Comprehensive analysis ofGut microbes · 2025
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  11. Microbial genomics · 2025
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  12. Antiaging Effect of 2-Foods (Basel, Switzerland) · 2025
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  13. Review
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  15. Article
  16. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 1 country.

Xiaozhe XiongDepartment 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.
Songhai TianDepartment 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.
Pan YangDepartment of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Francois LebretonDepartment 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 Surveillance Network (MRSN), Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Huan BaoDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA.
Kuanwei ShengWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.
Linxiang YinDepartment 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.
Pengsheng ChenDepartment 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.
Jie ZhangDepartment of Urology, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
Wanshu QiDivision of Endocrinology, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Jianbin RuanProgram 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.
Hao WuVascular Biology Program, Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Hong ChenVascular Biology Program, Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
David T BreaultDivision 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.
Hao WuProgram in Cellular and Molecular Medicine, Boston Children's Hospital, and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Ashlee M EarlBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Michael S GilmoreDepartment 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.edu.
Jonathan AbrahamDepartment 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.
Min DongDepartment 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.
Boston Children's Hospital · USHarvard University · USBroad Institute · USMassachusetts Eye and Ear Infirmary · USScripps Research Institute · US

Funding

Viral Genomics: evolution, spread, and host interactionsU19AI110818 · NIAID · BROAD INSTITUTE, INC. · PI NEAFSEY, DANIEL E · 2014 to 2024
$66.5M
Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI Suzanne Walker · 2009 to 2026
$39.4M
User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI Nozomi Ando, J Christopher Fromme · 2018 to 2026
$34.2M
STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2M
PROGRAM IN BLOOD COAGULATION AND VASCULAR BIOLOGYT32HL007917 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Robert C Flaumenhaft · 1999 to 2026
$11.1M
Structure and Function of C. Difficile ToxinsR01AI139087 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI Min Dong, Rongsheng Jin · 2018 to 2026
$7.4M
Epsin in Angiogenesis and Vascular RemodelingR01HL093242 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI CHEN, HONG, WANG, DA-ZHI · 2009 to 2021
$7.3M
Long-term effects of botulinum neurotoxins on neuronal viabilityR01NS080833 · NINDS · HARVARD MEDICAL SCHOOL · PI Min Dong · 2013 to 2026
$6.8M
GuMI: New In Vitro Platforms to Parse the Human Gut Epithelial-Microbiome-Immune AxisR01EB021908 · NIBIB · NORTHEASTERN UNIVERSITY · PI CARRIER, REBECCA L, GRIFFITH, LINDA G · 2016 to 2020
$5.2M
Mechanisms regulating VEGF receptors in diabetic angiogenesisR01HL130845 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, XU, JIAN · 2016 to 2023
$4.9M
Developing broad-spectrum therapeutics against C. difficile toxinsR01AI158503 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG · 2021 to 2025
$3.9M
NCRR NIH HHS S10 RR029205NHLBI NIH HHS R01 HL093242NHLBI NIH HHS R01 HL130845NHLBI NIH HHS R01 HL137229NHLBI NIH HHS R01 HL156362NHLBI NIH HHS T32 HL007917NIAID NIH HHS HHSN272200900018CNIAID NIH HHS P01 AI083214NIAID NIH HHS R01 AI132387NIAID NIH HHS R01 AI139087NIAID NIH HHS R01 AI158503NIAID NIH HHS U19 AI110818NIBIB NIH HHS R01 EB021908NICHD NIH HHS P30 HD018655NIDDK NIH HHS P30 DK034854NIGMS NIH HHS DP2 GM140920NIGMS NIH HHS P30 GM124165NINDS NIH HHS R01 NS080833NINDS NIH HHS R01 NS117626NINDS NIH HHS R21 NS106159
6 · The paper itself

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.

Indexed as

EnterococcusLeukocytes, MononuclearAnimalsBacterial ToxinsCattleHorsesMiceMicrobial Sensitivity TestsSwineVirulence FactorsBacterial ToxinsVirulence Factorsbacterial toxinCRISPR screenE. faecalisE. faeciumE. hiraeEnterococcusHLA-IinterferonMHC-Ipore-forming toxin

Identifiers

PMID35259335
PMCPMC8978092
OpenAlexW4221078486

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.