"Some phages carry molecular anchors that help them attach to human cells and even enter them."
— Gábor Apjok, co-first and co-corresponding author
Key Findings
- Molecular Anchors: Researchers identified phage surface proteins that act as molecular anchors, enabling the phages to attach to human cells.
- Genetic Transfer: Using genetic engineering, the team transferred these adhesion proteins to a phage that naturally lacks them. The engineered phages demonstrated enhanced binding to human cells, higher rates of intracellular entry, and extended retention in the gastrointestinal tract of mice compared to non-engineered phages.
- Intracellular Trafficking: Microscopy analysis revealed that internalized phages preferentially localize to the Golgi apparatus and the endoplasmic reticulum. These organelles are part of non-degradative cellular pathways, suggesting the phages may remain structurally intact while inside the cell.
- Prevalence in Healthy Gut Viromes: Genes encoding these adhesion proteins are common among dominant gut virome constituents and appear more abundant in healthy individuals, suggesting a potential ecological advantage for phages that carry them.
"Our results suggest that certain surface proteins may help [phages] not only pass through this environment, but also attach to it."
— Tóbiás Sári, co-first author
Implications
The findings challenge the traditional view of phages as viruses that exclusively infect bacteria. The study suggests that epithelial binding may be an evolutionarily advantageous strategy for phages, rather than a side effect of their presence in the gut. The research raises questions about the fate of internalized phages and their potential effects on cellular functions, gut homeostasis, immune modulation, and barrier integrity.
The study also has potential implications for phage therapy. Engineering phages with tailored adhesins could improve their targeting and retention in the body, potentially increasing their effectiveness against pathogenic bacteria, including antibiotic-resistant strains.
Methodology
The study integrated microscopy, microbial genomics, bioinformatics, and synthetic biology. Contributions came from multiple laboratories and disciplines. The lead author is Bálint Kintses of the Synthetic and Systems Biology Unit at the HUN-REN Biological Research Centre in Szeged, Hungary.
Publication Details
The paper is published in Nature Communications. The news release was dated June 4, 2026. Image credits: Gábor Apjok.