Intranasal phage treatment overcomes the limitations posed by antibody-mediated neutralization in bacteriophage therapy for Pseudomonas aeruginosa lung infections
Background: Our recent work discovered that intranasal inhalation of phage (KKP10) and Ca-EDTA substantially re-sensitized multidrug-resistant P. aeruginosa to ceftazidime/avibactam. Notably, the route of phage administration was reported to influence the development of antibody-mediated neutralizat...
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Elsevier
2024-12-01
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| Series: | Journal of Global Antimicrobial Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213716524004065 |
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| author | Dhammika Leshan Wannigama Cameron Hurst Peter N Monk Paul G. Higgins Tanittha Chatsuwan Anthony Kicic Parichart Hongsing Shuichi Abe Stephen M Stick |
| author_facet | Dhammika Leshan Wannigama Cameron Hurst Peter N Monk Paul G. Higgins Tanittha Chatsuwan Anthony Kicic Parichart Hongsing Shuichi Abe Stephen M Stick |
| author_sort | Dhammika Leshan Wannigama |
| collection | DOAJ |
| description | Background: Our recent work discovered that intranasal inhalation of phage (KKP10) and Ca-EDTA substantially re-sensitized multidrug-resistant P. aeruginosa to ceftazidime/avibactam. Notably, the route of phage administration was reported to influence the development of antibody-mediated neutralization of phage and thereby reducing its therapeutic efficiency. Therefore, we evaluated the effectiveness of KPP10 regimens utilizing systemic intraperitoneal (IP) and localized intranasal routes to treat chronic P. aeruginosa lung infection. Methods: The effectiveness of KPP10 regimens utilizing systemic intraperitoneal (IP) and localized intranasal routes to treat chronic P. aeruginosa lung infection, were access using mouse lung infection model togeter with ELISA to measured the production of neutralizing antibodies (IgM, IgG, and IgA). RESULTS: In this study, pre-treatment of mice with KPP10 intraperitoneally induced the systemic distribution of KPP10 to different internal organs, whereas intranasal KKP10 pre-treatment achieved significant KPP10 localization exclusively in alveolar space and elsewhere in lungs. Interestingly, intraperitoneal KPP10 administration regimens in chronic lung infection resulted in decreased survival with significant IgG, IgM, and IgA production. Meanwhile, after giving KPP10 regimens intranasally, anti-phage antibody production was undetectable and survival improved significantly. Conclusions: These results demonstrated that administering KPP10 directly to the lungs via the intranasal route could ensure a higher concentration of KPP10 at the infection site, expediting its bactericidal effects for increased pathogen elimination, while overcoming antibody-mediated phage neutralization and improving clinical outcomes in chronic pulmonary P. aeruginosa infections. |
| format | Article |
| id | doaj-art-63846fc9d88e492abf964bf30a10038c |
| institution | Kabale University |
| issn | 2213-7165 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Global Antimicrobial Resistance |
| spelling | doaj-art-63846fc9d88e492abf964bf30a10038c2024-12-27T04:08:51ZengElsevierJournal of Global Antimicrobial Resistance2213-71652024-12-013971Intranasal phage treatment overcomes the limitations posed by antibody-mediated neutralization in bacteriophage therapy for Pseudomonas aeruginosa lung infectionsDhammika Leshan Wannigama0Cameron Hurst1Peter N Monk2Paul G. Higgins3Tanittha Chatsuwan4Anthony Kicic5Parichart Hongsing6Shuichi Abe7Stephen M Stick8Department of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, JapanMolly Wardaguga Research Centre, Charles Darwin University, Queensland, AustraliaDepartment of Infection, Immunity & Cardiovascular Disease, University of Sheffield Medical School, United KingdomInstitute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyCenter of Excellence in Antimicrobial Resistance and Stewardship Research, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandSchool of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, AustraliaSchool of Integrative Medicine, Mae Fah Luang University, Chiang Rai, ThailandDepartment of Infectious Diseases and Infection Control, Yamagata Prefectural Central Hospital, Yamagata, JapanSchool of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, AustraliaBackground: Our recent work discovered that intranasal inhalation of phage (KKP10) and Ca-EDTA substantially re-sensitized multidrug-resistant P. aeruginosa to ceftazidime/avibactam. Notably, the route of phage administration was reported to influence the development of antibody-mediated neutralization of phage and thereby reducing its therapeutic efficiency. Therefore, we evaluated the effectiveness of KPP10 regimens utilizing systemic intraperitoneal (IP) and localized intranasal routes to treat chronic P. aeruginosa lung infection. Methods: The effectiveness of KPP10 regimens utilizing systemic intraperitoneal (IP) and localized intranasal routes to treat chronic P. aeruginosa lung infection, were access using mouse lung infection model togeter with ELISA to measured the production of neutralizing antibodies (IgM, IgG, and IgA). RESULTS: In this study, pre-treatment of mice with KPP10 intraperitoneally induced the systemic distribution of KPP10 to different internal organs, whereas intranasal KKP10 pre-treatment achieved significant KPP10 localization exclusively in alveolar space and elsewhere in lungs. Interestingly, intraperitoneal KPP10 administration regimens in chronic lung infection resulted in decreased survival with significant IgG, IgM, and IgA production. Meanwhile, after giving KPP10 regimens intranasally, anti-phage antibody production was undetectable and survival improved significantly. Conclusions: These results demonstrated that administering KPP10 directly to the lungs via the intranasal route could ensure a higher concentration of KPP10 at the infection site, expediting its bactericidal effects for increased pathogen elimination, while overcoming antibody-mediated phage neutralization and improving clinical outcomes in chronic pulmonary P. aeruginosa infections.http://www.sciencedirect.com/science/article/pii/S2213716524004065Antibody-mediated neutralizationBacteriophage treatmentPulmonary infectionPseudomonas aeruginosa |
| spellingShingle | Dhammika Leshan Wannigama Cameron Hurst Peter N Monk Paul G. Higgins Tanittha Chatsuwan Anthony Kicic Parichart Hongsing Shuichi Abe Stephen M Stick Intranasal phage treatment overcomes the limitations posed by antibody-mediated neutralization in bacteriophage therapy for Pseudomonas aeruginosa lung infections Journal of Global Antimicrobial Resistance Antibody-mediated neutralization Bacteriophage treatment Pulmonary infection Pseudomonas aeruginosa |
| title | Intranasal phage treatment overcomes the limitations posed by antibody-mediated neutralization in bacteriophage therapy for Pseudomonas aeruginosa lung infections |
| title_full | Intranasal phage treatment overcomes the limitations posed by antibody-mediated neutralization in bacteriophage therapy for Pseudomonas aeruginosa lung infections |
| title_fullStr | Intranasal phage treatment overcomes the limitations posed by antibody-mediated neutralization in bacteriophage therapy for Pseudomonas aeruginosa lung infections |
| title_full_unstemmed | Intranasal phage treatment overcomes the limitations posed by antibody-mediated neutralization in bacteriophage therapy for Pseudomonas aeruginosa lung infections |
| title_short | Intranasal phage treatment overcomes the limitations posed by antibody-mediated neutralization in bacteriophage therapy for Pseudomonas aeruginosa lung infections |
| title_sort | intranasal phage treatment overcomes the limitations posed by antibody mediated neutralization in bacteriophage therapy for pseudomonas aeruginosa lung infections |
| topic | Antibody-mediated neutralization Bacteriophage treatment Pulmonary infection Pseudomonas aeruginosa |
| url | http://www.sciencedirect.com/science/article/pii/S2213716524004065 |
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