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An enterococcal phage-derived enzyme suppresses graft-versus-host disease.

Authors :
Fujimoto K
Hayashi T
Yamamoto M
Sato N
Shimohigoshi M
Miyaoka D
Yokota C
Watanabe M
Hisaki Y
Kamei Y
Yokoyama Y
Yabuno T
Hirose A
Nakamae M
Nakamae H
Uematsu M
Sato S
Yamaguchi K
Furukawa Y
Akeda Y
Hino M
Imoto S
Uematsu S
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).)

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