Cryo-EM and cryo-ET reveal the molecular architecture and host interactions of mycobacteriophage Douge
Journal
Cell Reports
Journal Volume
44
Journal Issue
8
Start Page
116057
ISSN
2211-1247
Date Issued
2025-07-24
Author(s)
Maharana, Jitendra
Wang, Chun-Hsiung
Tsai, Li-An
Liao, Yi-Ting
Yang, Cheng-Han
Shen, Melvin C.
Macale, Lourriel S.
Tran, Thang Ngoc
Narsico, Joemark
Perez, Ronelito J.
Tewary, Sunil Kumar
Wu, Jian-Li
Lin, Hong-You
Franklin, Aaron
Moynihan, Patrick J.
Jacobs-Sera, Deborah
Freeman, Krista G.
Hatfull, Graham F.
Lowary, Todd L.
Ho, Meng-Chiao
Abstract
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.
Subjects
CP: Microbiology
CP: Molecular biology
cryo-EM
cryo-ET
lipoarabinomannan/arabinomannan
mycobacteriophage structure
phage-host interaction
Publisher
Elsevier BV
Type
journal article