Cryo-EM and cryo-ET reveal the molecular architecture and host interactions of mycobacteriophage Douge
Recent reports highlight the efficacy of engineered mycobacteriophages to treat non-tuberculosis mycobacterial disease. Molecular insights into mycobacteriophage architecture and host interactions could allow structure-guided phage engineering to increase efficacy and broaden host range, but such information is currently unavailable. We describe the cryoelectron microscopy (cryo-EM) structure of mycobacteriophage Douge, which contains 1,105 protein subunits assembled into a complete siphophage and is coated with glycan-binding domains for mycobacterial cell surface interactions. When filled with viral genome, the channel spanning the connector, tail, and baseplate is sealed by tape measure proteins, providing a genome gating system and requiring limited structural changes for genome ejection upon phage-host contact. Nanometer-resolution cryoelectron tomography (cryo-ET) snapshots of phage-host interactions show that the baseplate remains attached to the mycobacterial outer membrane during viral genome ejection. This study reveals high-resolution structural details of this mycobacteriophage and its interaction with host glycans.
Authors
- Patrick J. Moynihan (ORCID: https://orcid.org/0000-0003-4182-6223)
- Todd L. Lowary (ORCID: https://orcid.org/0000-0002-8331-8211)
- Sunil Kumar Tewary
- Aaron Franklin (ORCID: https://orcid.org/0009-0006-0472-5895)
- Ronelito J. Perez
- Meng‐Chiao Ho (ORCID: https://orcid.org/0000-0002-5424-4524)
- Jianli Wu (ORCID: https://orcid.org/0000-0003-0007-0554)
- Ming‐Ching Shen (ORCID: https://orcid.org/0000-0001-7789-2148)
- Yi‐Ting Liao (ORCID: https://orcid.org/0000-0001-5050-7481)
- Li-An Tsai
- Chun-Hsiung Wang (ORCID: https://orcid.org/0000-0003-2242-7200)
- Cheng‐Han Yang (ORCID: https://orcid.org/0000-0001-7517-3799)
- Jitendra Maharana (ORCID: https://orcid.org/0000-0003-4628-5956)
- Haijian Lin (ORCID: https://orcid.org/0000-0002-1337-6774)
- Shu‐Wei Chang (ORCID: https://orcid.org/0000-0003-0880-2385)
- Graham F. Hatfull (ORCID: https://orcid.org/0000-0002-6705-6821)
- Krista G. Freeman (ORCID: https://orcid.org/0000-0002-2944-5076)
- Trung Hieu Tran (ORCID: https://orcid.org/0000-0002-3989-4502)
- Deborah Jacobs-Sera
- Joemark T Narsico
- Lourriel S Macale
Institutions
- National Taiwan University (TW)
- University of Pittsburgh (US)
- Institute of Biological Chemistry, Academia Sinica (TW)
- Institute of Molecular Biology, Academia Sinica (TW)
- National Taipei University of Business (TW)
- University of Birmingham (GB)
- National Cheng Kung University (TW)
- National Taipei University (TW)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1016/j.celrep.2025.116057
- Citations
- 1
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 1.72
Funders
- Foundation for the National Institutes of Health
- Academia Sinica
- Ministry of Science and Technology, Taiwan
- National Institutes of Health