{
  "abstract": "The rise of antibiotic-resistant bacteria demands alternative therapeutic strategies, with bacteriophage (phage) therapy and phage-derived enzybiotics emerging as promising approaches. However, identifying candidate phages against specific pathogens has historically been a bottleneck due to the need for cultivation methods to assess host range and lytic activity. Advances in metagenomic sequencing and the emergence of large-scale viral genome databases now provide an opportunity to accelerate this process computationally. Here, we present a large-scale mining of the MetaVR database to identify phages targeting human bacterial pathogens. By integrating direct host associations with CRISPR-spacer evidence, we linked 196,472 high-quality and complete viral genomes, representing 42,360 vOTUs, to 618 species of pathogenic and opportunistic bacteria. Functional enrichment analysis revealed distinct genomic signatures with viral lifestyle and host-range breadth: virulent phages were enriched in replication and structural functions, whereas temperate and broad host-range phages were enriched in anti-defense and regulatory modules. To characterize their lytic potential we annotated lysis-related protein families and their structural diversity, identifying 76 structurally novel lysis-associated proteins, including candidates targeting WHO priority pathogens. Focused analysis of endolysins revealed 592 structural clusters, with extensive sharing of endolysin repertoires among ESKAPE pathogens, suggesting candidates for broad-spectrum enzybiotic development. Selection analysis identified 167 endolysin families with sites under positive selection within functional domains, highlighting evolutionary diversification potentially associated with phage-host interactions. Together, our results establish a large-scale framework for connecting human bacterial pathogens to phages and their lytic machinery, providing a resource for prioritizing phage therapy and enzybiotic development.",
  "abstract_shown": true,
  "affiliations": [
    "DOE Joint Genome Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "M. B. Fiamenghi"
    },
    {
      "affs": [
        0
      ],
      "name": "N. Kyrpides"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9kx7w4zt9hfm0.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748673",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748673v1.full",
  "id": "9kx7w4zt9hfm0",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748673v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "2303|Bacteriophages and microbial interactions"
    ]
  ],
  "openalex": "W7208813168",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748673v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9kx7w4zt9hfm0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "10.64898/2026.09.01.748673",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748673v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Discovery of novel enzybiotic candidates targeting human bacterial pathogens through large-scale viral-host profiling",
  "title_text": "Discovery of novel enzybiotic candidates targeting human bacterial pathogens through large-scale viral-host profiling",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/9kx7w4zt9hfm0",
  "venue": "bioRxiv",
  "versions": []
}