GVHD prevention with an E. faecalis-specific antibacterial enzyme after allo-HCT

Fujimoto K, Hayashi T, Yamamoto M, et al. An Enterococcal Phage-Derived Enzyme Suppresses Graft-Versus-Host Disease. Nature. 2024; (doi: 10.1038/s41586-024-07667-8).

Researchers believe treatment with an antibacterial enzyme specific to Enterococcus faecalis may provide prophylaxis against acute graft-versus-host disease (aGVHD). Disruptions to the gut microbiome, such as dysbiosis caused by expansion of E. faecalis in the intestine, are suspected in the development of aGVHD following allogeneic hematopoietic cell transplantation (allo-HCT). To learn more, investigators analyzed the intestinal microbiome of 46 allo-HCT recipients, with fecal samples from 30 containing levels of Enterococcus exceeding 25%. Further study revealed that in these cases of Enterococcus domination, E. faecalis forms biofilms that allow it to resist elimination via antibiotic treatment and instead proliferate in the intestine. Scientists subsequently identified endolysin, an antibacterial enzyme derived from E. faecalis-specific bacteriophages, which exhibits lytic behavior against these biofilms. In murine studies, a survival benefit was documented in gnotobiotic mice treated with the enzyme — compared with those that were not treated — after being colonized with E. faecalis or patient fecal samples heavily expressing Enterococcus. The evidence suggests that administering an E. faecalis-specific antibacterial enzyme after allo-HCT may prevent aGVHD.
Read More