Dhammika Leshan Wannigama, Jingping Shao, Hongya Sun, Yangzhong Wang, Cameron Hurst, Peter N Monk, Mohan Amarasiri, Phatthranit Phattharapornjaroen, William Graham Fox Ditcham, Thin Sandi Htun, Sirirat Luk-In, Yoshitaka Shimotai, Natharin Ngamwongsatit, Hitoshi Ishikawa, Naveen Kumar Devanga Ragupathi, Daniel Pletzer, Talerngsak Kanjanabuch, Aisha Khatib, Kazuhiko Miyanaga, Longzhu Cui, Kenji Shibuya, Paul G Higgins, Anthony Kicic, Parichart Hongsing, Jinxin Zhao, Shuichi Abe, Hiroshi Hamamoto
Archives of microbiology 207(12) 310-310 2025年10月18日
Phage therapy is a promising approach against multidrug-resistant infections, yet systemic administration can lead to incomplete cures. We investigated the distribution, immune responses, and efficacy of the therapeutic phage KPP10 delivered via intranasal or intraperitoneal (IP) routes in murine Pseudomonas aeruginosa lung infection models. Intranasal pre-treatment achieved markedly higher localization of KPP10 in the lungs and bronchoalveolar compartment compared to IP delivery. Intranasal administration elicited minimal systemic antibody responses, whereas IP injection triggered significant IgG, IgM, and IgA production. Antibody responses did not differ significantly between doses. In acute and chronic infection models, intranasal KPP10 significantly improved survival (p < 0.01) and reduced lung bacterial loads relative to IP injection. Importantly, IP treatment was associated with bacterial rebound after day 14 in chronic infection, whereas intranasal dosing sustained bacterial clearance. These findings demonstrate that intranasal delivery enhances pulmonary localization, minimizes antibody-mediated neutralization, and provides superior therapeutic efficacy, highlighting its potential as a more effective route for phage therapy against P. aeruginosa lung infections.