Back to Search
Start Over
An enterococcal phage-derived enzyme suppresses graft-versus-host disease.
- Source :
-
Nature [Nature] 2024 Aug; Vol. 632 (8023), pp. 174-181. Date of Electronic Publication: 2024 Jul 10. - Publication Year :
- 2024
-
Abstract
- Changes in the gut microbiome have pivotal roles in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogenic haematopoietic cell transplantation (allo-HCT) <superscript>1-6</superscript> . However, effective methods for safely resolving gut dysbiosis have not yet been established. An expansion of the pathogen Enterococcus faecalis in the intestine, associated with dysbiosis, has been shown to be a risk factor for aGVHD <superscript>7-10</superscript> . Here we analyse the intestinal microbiome of patients with allo-HCT, and find that E. faecalis escapes elimination and proliferates in the intestine by forming biofilms, rather than by acquiring drug-resistance genes. We isolated cytolysin-positive highly pathogenic E. faecalis from faecal samples and identified an anti-E. faecalis enzyme derived from E. faecalis-specific bacteriophages by analysing bacterial whole-genome sequencing data. The antibacterial enzyme had lytic activity against the biofilm of E. faecalis in vitro and in vivo. Furthermore, in aGVHD-induced gnotobiotic mice that were colonized with E. faecalis or with patient faecal samples characterized by the domination of Enterococcus, levels of intestinal cytolysin-positive E. faecalis were decreased and survival was significantly increased in the group that was treated with the E. faecalis-specific enzyme, compared with controls. Thus, administration of a phage-derived antibacterial enzyme that is specific to biofilm-forming pathogenic E. faecalis-which is difficult to eliminate with existing antibiotics-might provide an approach to protect against aGVHD.<br /> (© 2024. The Author(s).)
- Subjects :
- Adult
Aged
Animals
Female
Humans
Male
Mice
Middle Aged
Young Adult
Biofilms drug effects
Biofilms growth & development
Dysbiosis complications
Dysbiosis microbiology
Feces microbiology
Germ-Free Life
Hematopoietic Stem Cell Transplantation adverse effects
In Vitro Techniques
Intestines drug effects
Intestines microbiology
Perforin metabolism
Risk Factors
Transplantation, Homologous adverse effects
Whole Genome Sequencing
Drug Resistance, Bacterial drug effects
Anti-Bacterial Agents pharmacology
Bacteriophages enzymology
Bacteriophages genetics
Enterococcus faecalis drug effects
Enterococcus faecalis genetics
Enterococcus faecalis growth & development
Enterococcus faecalis metabolism
Enterococcus faecalis virology
Gastrointestinal Microbiome
Graft vs Host Disease complications
Graft vs Host Disease microbiology
Graft vs Host Disease prevention & control
Graft vs Host Disease therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 632
- Issue :
- 8023
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 38987594
- Full Text :
- https://doi.org/10.1038/s41586-024-07667-8