A bacteriophage may offer a new treatment for acute graft versus host disease (aGvHD), Japanese researchers have reported.
Reporting in Nature, the team identified an enzyme called endolysin expressed by a bacteriophage virus. They showed it has “potent” antibacterial activity against Enterococcus faecalis, a bacterial species believed to be associated with aGvHD.
The researchers at universities in Osaka and Tokyo began by examining the intestinal bacteriome of patients who received allogenic haematopoietic cell transplants. They report a predominance of enterococcal bacteria, in particular E. faecalis, which was especially prevalent in patients with acute leukaemia.
The scientists then conducted whole genome sequencing of E. faecalis and discovered the enzyme endolysin, derived from bacteriophages. With this enzyme, bacteriophages can break through biofilms that bacteria like E. faecalis create, and which are at the heart of their resistance to multiple antibiotics.
Further laboratory studies proved that endolysin could be an effective and specific treatment against E. faecalis. With laboratory mice, the team showed that purified endolysin specifically killed E. faecalis, suppressed the development of aGvHD, and improved survival.
Researcher Professor Kosuke Fujimoto, from Osaka Metropolitan University and The University of Tokyo, said: “Bacteriophage research is gaining momentum, with advancements in phage therapy paving the way for new treatments. Our discovery of the endolysin enzyme holds promise for future applications in preventing or treating acute GVHD.”
Source:
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. (2024) “An enterococcal phage-derived enzyme suppresses graft-versus-host disease.” Nature, 10 July 2024, doi: 10.1038/s41586-024-07667-8.
Link: https://www.nature.com/articles/s41586-024-07667-8
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