Bacteriophage-antibiotic combination therapy against extensively drug-resistant Pseudomonas aeruginosa infection to allow liver transplantation in a toddler

Journal article

: Growing antibiotic resistance has encouraged the revival of phage-inspired antimicrobial approaches. On the other hand, photodynamic therapy (PDT) is considered a very promising research domain for the protection against infectious diseases. Yet, very few efforts have been made to combine the advantages of both approaches in a modular, retargetable platform. Here, we foster the M13 bacteriophage as a multifunctional scaffold, enabling the selective photodynamic killing of bacteria. We took advantage of the well-defined molecular biology of M13 to functionalize its capsid with hundreds of photo-activable Rose Bengal sensitizers and contemporarily target this light-triggerable nanobot to specific bacterial species by phage display of peptide targeting moieties fused to the minor coat protein pIII of the phage. Upon light irradiation of the specimen, the targeted killing of diverse Gram(-) pathogens occurred at subnanomolar concentrations of the phage vector. Our findings contribute to the development of antimicrobials based on targeted and triggerable phage-based nanobiotherapeutics

Authors: Van Nieuwenhuyse, B; Van der Linden, D; Chatzis, O; Lood, C; Wagemans, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 13
• Issue: 1
• Pages: 5725
• Article number: 5725
• Publication date: 2022-09-29
• DOI: 10.1038/s41467-022-33294-w
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Bacteria; Biology; Virology; Sepsis; Pseudomonas aeruginosa; Phage therapy; Microbiology; Antibiotics; Antibiotic resistance; Medicine; Immunology; Bacteriophage; Internal medicine; Liver transplantation; Transplantation; Drug resistance