INTRODUCTION
Pseudomonas aeruginosa is a notorious Gram-negative opportunistic pathogen, known for its intrinsic resistance mechanisms and adaptability in hostile environments, particularly in clinical settings. The emergence of multidrug-resistant (MDR) strains has significantly limited treatment options and increased the need for alternative therapeutic strategies. Bacteriophage therapy has re-emerged as a viable approach, especially in targeting antibiotic-resistant pathogens. This study introduces phiLCL12, a novel bacteriophage isolated from hospital wastewater, with the potential to address this growing challenge. By integrating morphological, genomic, and functional assessments, the study explores the bacteriophage’s effectiveness in targeting MDR P. aeruginosa strains, especially in the context of biofilm-related infections. Through a comprehensive approach combining in vitro and in vivo analyses, the research sheds light on the potential synergy between phiLCL12 and conventional antibiotics, offering a new direction in combating resistant infections.
MORPHOLOGICAL AND GENOMIC CHARACTERIZATION
The bacteriophage phiLCL12 was isolated from hospital wastewater and characterized using transmission electron microscopy (TEM), which revealed a long contractile tail structure, typical of the Myoviridae family. Genomic sequencing and analysis via PhaGCN2 and whole genome-based taxonomy tools confirmed its classification under the Pbunavirus genus. This morphological and phylogenetic classification provides a foundational understanding of the phage’s structural attributes and evolutionary lineage. The presence of genetic elements supportive of its lytic lifecycle, rather than lysogenic, further strengthens its candidacy as a therapeutic agent. The genomic profile lacked known antibiotic resistance or virulence genes, an essential prerequisite for clinical application.
HOST RANGE AND ADSORPTION EFFICIENCY
A critical factor in phage therapy is the host range, and phiLCL12 demonstrated a broad host spectrum, effectively lysing 82.22% of tested P. aeruginosa clinical isolates. This wide host range enhances its therapeutic utility across diverse clinical cases. Adsorption assays indicated that up to 98% of target cells were bound within 4 minutes, reflecting the high binding efficiency of phiLCL12 to its host bacteria. These characteristics imply that phiLCL12 can rapidly interact with and infect MDR P. aeruginosa, making it an efficient tool for prompt bacterial clearance in infection sites, including biofilm-dense environments.
PHAGE EFFICACY AT VARYING MOIs
The lytic ability of phiLCL12 was evaluated at multiple multiplicities of infection (MOIs), demonstrating consistent effectiveness against MDR P. aeruginosa strains. Remarkably, both high and low MOI conditions resulted in substantial bacterial lysis, underscoring the robustness of this phage in different treatment scenarios. This property is essential for clinical translation, where precise dosing may vary based on infection load and site. The consistency of its antibacterial action across a range of MOIs supports its versatility and reliability as a therapeutic candidate.
SYNERGY WITH IMIPENEM AND BIOFILM INHIBITION
Biofilms present a formidable challenge in treating P. aeruginosa infections, often rendering antibiotics ineffective. In vitro experiments revealed that when phiLCL12 was combined with sub-inhibitory concentrations of imipenem, there was a significant inhibition of biofilm formation and enhanced clearance of established biofilms. This synergistic effect, known as phage–antibiotic synergy (PAS), suggests that phiLCL12 may disrupt biofilm architecture, enabling better antibiotic penetration and activity. These results highlight the phage’s potential to restore the effectiveness of antibiotics against biofilm-associated infections and improve clinical outcomes.
IN VIVO VALIDATION USING ZEBRAFISH MODEL
To evaluate therapeutic efficacy in a living system, the study employed a zebrafish infection model. Results demonstrated that the combination of phiLCL12 and imipenem significantly improved survival rates compared to antibiotic treatment alone. This in vivo validation reinforces the in vitro findings and provides critical preclinical evidence for the therapeutic potential of phage–antibiotic combinations. The zebrafish model, known for its translational relevance and immune system similarities to humans, provides a compelling case for the continued development of phiLCL12 as part of a phage-based therapeutic strategy.
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#BacteriophageTherapy #PseudomonasAeruginosa #AntibioticResistance #PhageResearch #BiofilmInhibition #PhageAntibioticSynergy #MultidrugResistance #HospitalWastewater #ZebrafishModel #PhageGenomics #MDRInfections #PhageImipenemCombo #PhageMorphology #TEMImaging #PhageHostRange #MOIEffectiveness #ClinicalPhageUse #Pbunavirus #BiofilmEradication #AlternativeTherapies
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