{ "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.\n\nDrug-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.", "abstract_shown": true, "affiliations": [ "Institute 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", "Department of Physics, Shaoyang University, Shaoyang, China", "GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, Guangzhou, China", "Department of Gastroenterology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China", "College of Elementary Education, Changsha Normal University, Changsha, China" ], "article_type": "Research Article", "arxiv": null, "author_total": 9, "authors": [ { "affs": [ 0, 1 ], "name": "Hao Pang" }, { "affs": [ 0 ], "name": "Yuan Chen" }, { "affs": [ 0 ], "name": "Zeng Peng" }, { "affs": [ 0 ], "name": "Hao Xiao" }, { "affs": [ 0 ], "name": "Wenyuan Chen" }, { "affs": [ 1 ], "name": "Xiaowu Li" }, { "affs": [ 2, 3 ], "name": "Ping Chen" }, { "affs": [ 0, 4 ], "name": "Jing Zheng" }, { "affs": [ 0 ], "name": "Hongrong Liu", "orcid": "0000-0001-6247-5464" } ], "bibtex": "https://research.draconitic.com/paper/0k3wv66172a13.bib", "cited_by": 0, "doi": "10.1371/journal.pbio.3004081", "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004081", "id": "0k3wv66172a13", "issns": [ "1545-7885", "1544-9173" ], "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004081", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Bacteria" ], [ "heading", "Bacterial Pathogens" ], [ "heading", "Bacteriophages" ], [ "heading", "Biochemistry" ], [ "heading", "Biological Databases" ], [ "heading", "Biology and Life Sciences" ], [ "heading", "Chemistry" ], [ "heading", "Database and Informatics Methods" ], [ "heading", "Dimers" ], [ "heading", "Electron Cryo-Microscopy" ], [ "heading", "Electron Microscopy" ], [ "heading", "Macromolecular Structure Analysis" ], [ "heading", "Materials" ], [ "heading", "Materials Science" ], [ "heading", "Medical Microbiology" ], [ "heading", "Medicine and Health Sciences" ], [ "heading", "Microbial Pathogens" ], [ "heading", "Microbiology" ], [ "heading", "Microscopy" ], [ "heading", "Molecular Biology" ], [ "heading", "Monomers" ], [ "heading", "Oligomers" ], [ "heading", "Organisms" ], [ "heading", "Pathogens" ], [ "heading", "Pathology and Laboratory Medicine" ], [ "heading", "Physical Sciences" ], [ "heading", "Polymer Chemistry" ], [ "heading", "Protein Domains" ], [ "heading", "Protein Structure" ], [ "heading", "Protein Structure Databases" ], [ "heading", "Proteins" ], [ "heading", "Pseudomonas" ], [ "heading", "Pseudomonas Aeruginosa" ], [ "heading", "Research Article" ], [ "heading", "Research and Analysis Methods" ], [ "heading", "Viral Packaging" ], [ "heading", "Viral Replication" ], [ "heading", "Virology" ], [ "heading", "Viruses" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Protein domains" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Protein structure/Protein structure databases" ], [ "plos", "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens/Pseudomonas aeruginosa" ], [ "plos", "/Biology and life sciences/Microbiology/Virology/Viral replication/Viral packaging" ], [ "plos", "/Biology and life sciences/Molecular biology/Macromolecular structure analysis/Protein structure/Protein structure databases" ], [ "plos", "/Biology and life sciences/Organisms/Bacteria/Pseudomonas/Pseudomonas aeruginosa" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/Bacteriophages" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens/Pseudomonas aeruginosa" ], [ "plos", "/Physical sciences/Chemistry/Polymer chemistry/Dimers" ], [ "plos", "/Physical sciences/Chemistry/Polymer chemistry/Monomers" ], [ "plos", "/Physical sciences/Materials science/Materials/Oligomers/Dimers" ], [ "plos", "/Research and analysis methods/Database and informatics methods/Biological databases/Protein structure databases" ], [ "plos", "/Research and analysis methods/Microscopy/Electron microscopy/Electron cryo-microscopy" ] ], "openalex": null, "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3004081&type=printable", "pmcid": "PMC13730344", "pmid": "42976175", "published": "2026-11-01", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/0k3wv66172a13.ris", "sources": [ { "first_seen": "2026-11-04T12:20:43Z", "native_id": "10.1371/journal.pbio.3004081", "source": "plos", "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004081" }, { "first_seen": "2026-11-04T15:20:46Z", "native_id": "PMC:PMC13730344", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13730344" }, { "first_seen": "2026-11-07T12:22:55Z", "native_id": "PMC13730344", "source": "pmc", "url": "https://doi.org/10.1371/journal.pbio.3004081" } ], "subjects": [ { "field": "biochemistry", "origin": "heading:Molecular Biology", "subfield": "molecular-biology" }, { "field": "biology", "origin": "plos:microbiology", "subfield": "microbiology" }, { "field": "chemistry", "origin": "plos:polymer chemistry", "subfield": "materials-polymers" }, { "field": "medicine", "origin": "heading:Medicine and Health Sciences", "subfield": "general" } ], "title": "A split nozzle and two-protein chain-like fibers define the tail architecture of Pseudomonas aeruginosa podophage A1002", "title_text": "A split nozzle and two-protein chain-like fibers define the tail architecture of Pseudomonas aeruginosa podophage A1002", "type": "peer-reviewed", "updated_at": "2026-11-07T12:22:55Z", "url": "https://research.draconitic.com/paper/0k3wv66172a13", "venue": "PLOS Biology", "versions": [] }