Acute graft-versus-host disease (aGVHD) happens when donated immune cells attack the recipient’s tissues post an allogeneic hematopoietic stem cell transplant (allo-HCT). Researchers have found an endolysin derived from a bacteriophage that can target biofilms made by Enterococcus faecalis, offering hope for customized interventions in allo-HCT.
Allogeneic hematopoietic cell transplantation (allo-HCT) involves transferring healthy donor stem cells to patients with conditions like blood cancer or certain genetic blood disorders. It often results in acute graft-versus-host disease (aGVHD), where the donor’s immune cells attack the recipient’s tissues. Recent studies emphasize the role of the microbiome in aGVHD, with dysbiosis contributing to its development. Dysbiosis can lead to the growth of pathogenic commensal bacteria, such as Enterococcus species like E. faecalis and E. faecium, which are linked to drug-resistant infections. However, there is a lack of efficient therapies directed at treating dysbiosis in aGVHD.
To fill this gap, a team led by Associate Professor Kosuke Fujimoto from Osaka Metropolitan University and The University of Tokyo, along with Professor Seiya Imoto from The University of Tokyo, and Satoshi Uematsu from Osaka Metropolitan University and The University of Tokyo, studied the gut bacteriome of allo-HCT patients. They aimed to examine the prevalence and effects of Enterococcus domination in this patient group. Published in the journal Nature on July 10, 2024, their research sheds light on crucial microbiota dynamics in allo-HCT.
Explaining the study’s rationale, Fujimoto states, “During dysbiosis, symbiotic commensal bacteria can become pathogenic, leading to disease progression. Considering the specificity of phage therapy and its ability to spare beneficial bacteria, we focused on phage-derived lytic enzymes.”
The team began by studying the intestinal microbiome of allo-HCT patients and observed a dominance of Enterococcus species, specifically E. faecalis, notably linked to acute leukemia. While E. faecalis strains were sensitive to antibiotics, they harbored genes associated with virulence. Metagenomic analysis indicated genetic markers related to biofilm formation. Whole-genome sequencing of E. faecalis revealed the presence of a bacteriophage-derived enzyme, endolysin, with potent antibacterial properties against E. faecalis.
Fujimoto’s team conducted in-vitro and in-vivo tests to confirm the endolysin’s effectiveness. The enzyme successfully targeted E. faecalis and disrupted biofilms without affecting other gut bacteria. In mouse models, endolysin treatment reduced E. faecalis colonization and aGVHD development, showing promise for potential future applications in preventing or treating the disease.
The discovery of endolysin from bacteriophage introduces a new class of therapeutic compounds to combat highly resistant, biofilm-forming bacteria, thanks to the research team’s efforts!
