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

Area of Science:

• Microbiology
• Immunology
• Transplantation Science

Background:

• Gut microbiome dysbiosis is implicated in acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplantation (allo-HCT).
• Expansion of Enterococcus faecalis, a pathogen associated with dysbiosis, is a known risk factor for aGVHD.
• Current methods for resolving gut dysbiosis post-allo-HCT remain limited.

Purpose of the Study:

• To investigate the mechanism of Enterococcus faecalis proliferation in the gut of allo-HCT patients.
• To identify and characterize a novel therapeutic agent against pathogenic E. faecalis.
• To evaluate the efficacy of this agent in preventing or treating aGVHD.

Main Methods:

• Analysis of intestinal microbiome in allo-HCT patients.
• Isolation of pathogenic, cytolysin-positive E. faecalis strains.
• Identification of a bacteriophage-derived enzyme with anti-E. faecalis activity.
• In vitro and in vivo testing of the enzyme's lytic activity against E. faecalis biofilms.
• Assessment of the enzyme's therapeutic effect in aGVHD-induced gnotobiotic mouse models.

Main Results:

• E. faecalis proliferates by forming biofilms, not through drug resistance.
• A specific bacteriophage-derived enzyme demonstrated potent lytic activity against E. faecalis biofilms.
• Treatment with this enzyme significantly reduced intestinal E. faecalis levels and increased survival in aGVHD mouse models.

Conclusions:

• Phage-derived enzymes targeting biofilm-forming E. faecalis offer a novel therapeutic strategy.
• This approach may protect against aGVHD by controlling pathogenic gut bacteria.
• This represents a potential advancement in managing complications after allo-HCT.