Augmenting phage therapy using green nanotechnology for promising infection control, wound healing and devoiding phage resistance in MDR Pseudomonas aeruginosa

Abstract Humanity could descend into a pre-antibiotic world as a result of antimicrobial resistance (AMR). Phage defenses are considered “vintage heroes” in the battle against multidrug-resistant (MDR) bacteria. However, phage resistance continues to evolve, necessitating alternative strategies. A p...

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Main Authors: Abishek Mani, Aarcha Shanmugha Mary, Nashath Kalangadan, Srivignesh Sundaresan, Somnath Ghosh, John Prakash, Siva Sundara Kumar Durairajan, Kaushik Rajaram
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-00449-w
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author Abishek Mani
Aarcha Shanmugha Mary
Nashath Kalangadan
Srivignesh Sundaresan
Somnath Ghosh
John Prakash
Siva Sundara Kumar Durairajan
Kaushik Rajaram
author_facet Abishek Mani
Aarcha Shanmugha Mary
Nashath Kalangadan
Srivignesh Sundaresan
Somnath Ghosh
John Prakash
Siva Sundara Kumar Durairajan
Kaushik Rajaram
author_sort Abishek Mani
collection DOAJ
description Abstract Humanity could descend into a pre-antibiotic world as a result of antimicrobial resistance (AMR). Phage defenses are considered “vintage heroes” in the battle against multidrug-resistant (MDR) bacteria. However, phage resistance continues to evolve, necessitating alternative strategies. A potential solution is combining phages with antimicrobials like silver nanoparticles (AgNPs) to enhance the phage therapy. This study focuses on a combination therapy using Bauhinia variegata L.-mediated AgNPs and Pseudomonas phage M12PA to target multidrug-resistant (MDR) Pseudomonas aeruginosa. The antibacterial properties of this combination were evaluated through comprehensive characterizations and assays. As a proof of concept, the AgNP-phage combination delayed phage resistance by 6–12 h, reduced mutation, and enhanced antibacterial efficiency. Anti-biofilm activity improved by ~ 40% compared to AgNPs alone at sub-inhibitory concentrations. AgNPs and phages have demonstrated excellent compatibility, and the phage titer did not drop noticeably over 30 days. Biocompatibility assessments, including cell viability and hemolysis assays, highlighted the safety of biosynthesized AgNPs. Wound healing efficacy was also demonstrated in mouse fibroblast cells and an in ovo angiogenesis model. This study underscores the efficiency of phage-AgNPs synergy to be a potential therapeutic approach for MDR bacterial wound infection, showing effective anti-biofilm activity, delayed phage resistance, and minimal toxicity.
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spelling doaj-art-e49c49fe1445422ab166e4e2b6c7289e2025-08-24T11:24:31ZengNature PortfolioScientific Reports2045-23222025-08-0115111610.1038/s41598-025-00449-wAugmenting phage therapy using green nanotechnology for promising infection control, wound healing and devoiding phage resistance in MDR Pseudomonas aeruginosaAbishek Mani0Aarcha Shanmugha Mary1Nashath Kalangadan2Srivignesh Sundaresan3Somnath Ghosh4John Prakash5Siva Sundara Kumar Durairajan6Kaushik Rajaram7Department of Microbiology, Central University of Tamil NaduDepartment of Microbiology, Central University of Tamil NaduDepartment of Microbiology, Central University of Tamil NaduDepartment of Horticulture, Central University of Tamil NaduDepartment of Humanities and Sciences, Indian Institute of Petroleum and Energy (IIPE)Department of Chemistry, Central University of Tamil NaduDepartment of Microbiology, Central University of Tamil NaduDepartment of Microbiology, Central University of Tamil NaduAbstract Humanity could descend into a pre-antibiotic world as a result of antimicrobial resistance (AMR). Phage defenses are considered “vintage heroes” in the battle against multidrug-resistant (MDR) bacteria. However, phage resistance continues to evolve, necessitating alternative strategies. A potential solution is combining phages with antimicrobials like silver nanoparticles (AgNPs) to enhance the phage therapy. This study focuses on a combination therapy using Bauhinia variegata L.-mediated AgNPs and Pseudomonas phage M12PA to target multidrug-resistant (MDR) Pseudomonas aeruginosa. The antibacterial properties of this combination were evaluated through comprehensive characterizations and assays. As a proof of concept, the AgNP-phage combination delayed phage resistance by 6–12 h, reduced mutation, and enhanced antibacterial efficiency. Anti-biofilm activity improved by ~ 40% compared to AgNPs alone at sub-inhibitory concentrations. AgNPs and phages have demonstrated excellent compatibility, and the phage titer did not drop noticeably over 30 days. Biocompatibility assessments, including cell viability and hemolysis assays, highlighted the safety of biosynthesized AgNPs. Wound healing efficacy was also demonstrated in mouse fibroblast cells and an in ovo angiogenesis model. This study underscores the efficiency of phage-AgNPs synergy to be a potential therapeutic approach for MDR bacterial wound infection, showing effective anti-biofilm activity, delayed phage resistance, and minimal toxicity.https://doi.org/10.1038/s41598-025-00449-wPhage therapyBiosynthesized AgNPsAnti-biofilm activityDelayed phage resistanceIn ovo angiogenesisIn ovo infection model
spellingShingle Abishek Mani
Aarcha Shanmugha Mary
Nashath Kalangadan
Srivignesh Sundaresan
Somnath Ghosh
John Prakash
Siva Sundara Kumar Durairajan
Kaushik Rajaram
Augmenting phage therapy using green nanotechnology for promising infection control, wound healing and devoiding phage resistance in MDR Pseudomonas aeruginosa
Scientific Reports
Phage therapy
Biosynthesized AgNPs
Anti-biofilm activity
Delayed phage resistance
In ovo angiogenesis
In ovo infection model
title Augmenting phage therapy using green nanotechnology for promising infection control, wound healing and devoiding phage resistance in MDR Pseudomonas aeruginosa
title_full Augmenting phage therapy using green nanotechnology for promising infection control, wound healing and devoiding phage resistance in MDR Pseudomonas aeruginosa
title_fullStr Augmenting phage therapy using green nanotechnology for promising infection control, wound healing and devoiding phage resistance in MDR Pseudomonas aeruginosa
title_full_unstemmed Augmenting phage therapy using green nanotechnology for promising infection control, wound healing and devoiding phage resistance in MDR Pseudomonas aeruginosa
title_short Augmenting phage therapy using green nanotechnology for promising infection control, wound healing and devoiding phage resistance in MDR Pseudomonas aeruginosa
title_sort augmenting phage therapy using green nanotechnology for promising infection control wound healing and devoiding phage resistance in mdr pseudomonas aeruginosa
topic Phage therapy
Biosynthesized AgNPs
Anti-biofilm activity
Delayed phage resistance
In ovo angiogenesis
In ovo infection model
url https://doi.org/10.1038/s41598-025-00449-w
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