A split nozzle and two-protein chain-like fibers define the tail architecture of Pseudomonas aeruginosa podophage A1002
5 affiliations
- 1Institute of Interdisciplinary Studies, Key Laboratory for Matter Microstructure and Function of Hunan Province, Key Laboratory of Low-dimensional Quantum Structures and Quantum Control, School of Physics and Electronics, Hunan Normal University, Changsha, China
- 2Department of Physics, Shaoyang University, Shaoyang, China
- 3GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, Guangzhou, China
- 4Department of Gastroenterology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
- 5College of Elementary Education, Changsha Normal University, Changsha, China
Abstract
Phage therapy offers unique advantages against antibiotic-resistant bacteria. However, high-resolution structural studies of phages targeting Pseudomonas aeruginosa—a top-seven global pathogen—particularly podophages, remain severely limited, directly impeding structure-based development of novel antimicrobials. In this study, we utilize cryo-EM to resolve the high-resolution intact structure of mature phage A1002, a podophage infecting carbapenem-resistant P. aeruginosa. Based on density maps combined with AlphaFold3 predictions, we identified 11 structural protein components from the head to the tail. Phage A1002 exhibits a distinctly elongated tail morphology distinct from other reported podophages. Notably, the A1002 nozzle employs a distinct assembly strategy, featuring the unique nozzle-rope protein and nozzle-base protein, which may have evolved through modular evolution and horizontal gene transfer. Furthermore, the nozzle-rope protein provides 11 adsorption sites for fiber dimers, and these dimers are assembled from two proteins, giving rise to two types of dimers: dimers 1–7 correspond to fiber I (gp40), and dimers 8–11 correspond to fiber II (gp41). The nozzle-rope protein and these dimers combine to form a chain-like fiber. The tail tube comprises a double-layered, elongated tube structure that functions to simultaneously increase tail length and provide docking sites for six chain-like fibers. These distinctive structural features provide the molecular basis for A1002’s broad-spectrum infection of drug-resistant P. aeruginosa and offer a novel molecular blueprint for rational design of structure-guided phage therapeutics.
Drug-resistant Pseudomonas aeruginosa is difficult to treat, and its phages remain poorly understood. This study shows that the podophage A1002 has an unusual tail architecture that offers a blueprint for structure-guided antimicrobial design.
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BibTeX
@article{pang2026split,
title = {{A split nozzle and two-protein chain-like fibers define the tail architecture of Pseudomonas aeruginosa podophage A1002}},
author = {Hao Pang and Yuan Chen and Zeng Peng and Hao Xiao and Wenyuan Chen and Xiaowu Li and Ping Chen and Jing Zheng and Hongrong Liu},
journal = {PLOS Biology},
year = {2026},
month = nov,
doi = {10.1371/journal.pbio.3004081},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004081},
note = {CC BY},
}
RIS
TY - JOUR
TI - A split nozzle and two-protein chain-like fibers define the tail architecture of Pseudomonas aeruginosa podophage A1002
AU - Hao Pang
AU - Yuan Chen
AU - Zeng Peng
AU - Hao Xiao
AU - Wenyuan Chen
AU - Xiaowu Li
AU - Ping Chen
AU - Jing Zheng
AU - Hongrong Liu
PY - 2026
DA - 2026/11/01
JO - PLOS Biology
DO - 10.1371/journal.pbio.3004081
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004081
AB - Phage therapy offers unique advantages against antibiotic-resistant bacteria. However, high-resolution structural studies of phages targeting Pseudomonas aeruginosa—a top-seven global pathogen—particularly podophages, remain severely limited, directly impeding structure-based development of novel antimicrobials. In this study, we utilize cryo-EM to resolve the high-resolution intact structure of mature phage A1002, a podophage infecting carbapenem-resistant P. aeruginosa. Based on density maps combined with AlphaFold3 predictions, we identified 11 structural protein components from the head to the tail. Phage A1002 exhibits a distinctly elongated tail morphology distinct from other reported podophages. Notably, the A1002 nozzle employs a distinct assembly strategy, featuring the unique nozzle-rope protein and nozzle-base protein, which may have evolved through modular evolution and horizontal gene transfer. Furthermore, the nozzle-rope protein provides 11 adsorption sites for fiber dimers, and these dimers are assembled from two proteins, giving rise to two types of dimers: dimers 1–7 correspond to fiber I (gp40), and dimers 8–11 correspond to fiber II (gp41). The nozzle-rope protein and these dimers combine to form a chain-like fiber. The tail tube comprises a double-layered, elongated tube structure that functions to simultaneously increase tail length and provide docking sites for six chain-like fibers. These distinctive structural features provide the molecular basis for A1002’s broad-spectrum infection of drug-resistant P. aeruginosa and offer a novel molecular blueprint for rational design of structure-guided phage therapeutics. Drug-resistant Pseudomonas aeruginosa is difficult to treat, and its phages remain poorly understood. This study shows that the podophage A1002 has an unusual tail architecture that offers a blueprint for structure-guided antimicrobial design.
SN - 1545-7885
SN - 1544-9173
ER -