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Peer-reviewedCC BY 4.0Nature Microbiology

Systematic mapping of bacteriophage gene essentiality with HIDEN-SEQ

  • Dorentina Humolli1
  • Damien Piel1
  • Jessica Ransome1
  • Kathrin Bausch2
  • Sarah Tschudin‐Sutter3
  • Monica Ortelli4
  • Christoph Dehio4
  • Jan‐Willem Veening5
  • Alexander Harms6
6 affiliations
  1. 1Department of Health Sciences and Technology, Institute of Food, Nutrition, and Health, ETH Zürich, Zurich, Switzerland
  2. 2Department of Urology, University Hospital Basel, Basel, Switzerland
  3. 3Division of Infectious Diseases, Department of Clinical Research, University Hospital Basel, Basel, Switzerland
  4. 4Biozentrum, University of Basel, Basel, Switzerland
  5. 5Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
  6. 6Department of Health Sciences and Technology, Institute of Food, Nutrition, and Health, ETH Zürich, Zurich, Switzerland. [email protected]
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Abstract

The arms race of bacteriophages and their bacterial hosts has inspired major breakthroughs in biotechnology and shaped phages as fierce predators with great clinical potential to fight multidrug-resistant bacterial pathogens. However, the large amount of genes of unknown function in phage genomes remains a major obstacle for the molecular understanding of phage–host interactions. Here we present HIDEN-SEQ (hidden Acr-enabled transposon-insertion sequencing), a transposon-insertion sequencing method for phages that systematically links viral genes to selectable phenotypes. Using model phage T4, we show that HIDEN-SEQ readily reproduces the gene essentiality map established over decades of research. Our method is easily portable across diverse non-model phages and reveals conditionally essential genes in multiple bacterial hosts and growth conditions, including previously unknown antidefence factors that we matched to specific antiviral defences. We anticipate that HIDEN-SEQ will be leveraged to reveal functions of viral genes with direct relevance for microbial ecology, biotechnology and phage therapy.

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Cite

BibTeXRIS
BibTeX
@article{humolli2026systematic,
  title = {{Systematic mapping of bacteriophage gene essentiality with HIDEN-SEQ}},
  author = {Dorentina Humolli and Damien Piel and Jessica Ransome and Kathrin Bausch and Sarah Tschudin‐Sutter and Monica Ortelli and Christoph Dehio and Jan‐Willem Veening and Alexander Harms},
  journal = {Nature Microbiology},
  year = {2026},
  month = sep,
  doi = {10.1038/s41564-026-02455-8},
  url = {https://doi.org/10.1038/s41564-026-02455-8},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Systematic mapping of bacteriophage gene essentiality with HIDEN-SEQ
AU  - Dorentina Humolli
AU  - Damien Piel
AU  - Jessica Ransome
AU  - Kathrin Bausch
AU  - Sarah Tschudin‐Sutter
AU  - Monica Ortelli
AU  - Christoph Dehio
AU  - Jan‐Willem Veening
AU  - Alexander Harms
PY  - 2026
DA  - 2026/09/25
JO  - Nature Microbiology
DO  - 10.1038/s41564-026-02455-8
UR  - https://doi.org/10.1038/s41564-026-02455-8
AB  - The arms race of bacteriophages and their bacterial hosts has inspired major breakthroughs in biotechnology and shaped phages as fierce predators with great clinical potential to fight multidrug-resistant bacterial pathogens. However, the large amount of genes of unknown function in phage genomes remains a major obstacle for the molecular understanding of phage–host interactions. Here we present HIDEN-SEQ (hidden Acr-enabled transposon-insertion sequencing), a transposon-insertion sequencing method for phages that systematically links viral genes to selectable phenotypes. Using model phage T4, we show that HIDEN-SEQ readily reproduces the gene essentiality map established over decades of research. Our method is easily portable across diverse non-model phages and reveals conditionally essential genes in multiple bacterial hosts and growth conditions, including previously unknown antidefence factors that we matched to specific antiviral defences. We anticipate that HIDEN-SEQ will be leveraged to reveal functions of viral genes with direct relevance for microbial ecology, biotechnology and phage therapy.
SN  - 2058-5276
ER  -