Efficacy and Safety of a novel virulent phage against acute pulmonary infection of Acinetobacter baumanniii in mice

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Efficacy and Safety of a novel virulent phage against acute pulmonary infection of Acinetobacter baumanniii in mice

Authors

Wang, J.; Hu, H.; Zhu, T.; Ren, X.; Jiang, W.; Hou, X.; Lin, J.; Yu, X.

Abstract

Background: Acinetobacter baumanniii (A.baumannii) is an opportunistic pathogen that significantly contributes to the burden of hospital-acquired infections. The treatment of multidrug-resistant A.baumannii poses a major challenge due to its resistance to multiple antibiotics. Phage therapy, leveraging bacteriophages as natural bacterial predators, has re-emerged as a promising approach to combat antibiotic-resistant infections. Objectives: This study aimed to isolate and characterize phages targeting A.baumannii from environmental samples, establish a comprehensive phage characterization process, and evaluate the therapeutic efficacy and safety of this phage using a mouse model with pneumonia. Methods: The following are the methods used for this study. Results: This study identified vB_AbaS_qsb1,a novel virulent phage which had never been reported that specifically lyses A.baumannii. The vB_AbaS_qsb1 exhibits robust stability across a broad temperature and pH range, a short incubation period. Genomic analysis showed that qsb1 has a 54,713 bp dsDNA genome with a GC content of 39%,lacking any known virulent factor or antibiotic resistance genes. Importantly, safety evaluations demonstrated that high-dose vB_AbaS_qsb1 did not induce any adverse clinical symptoms in mice, further underscoring the phage,s excellent safety profile as confirmed by other experimental results. Therapeutic experiments showed that vB_AbaS_qsb1 provided at least 50% protection against acute pneumonia causing by A.baumannii, with a significant reduction in lungs, bacterial loads and sustained high phage titers. Inflammatory markers in phage-treated mice were significantly lower than those in untreated groups, underscoring the phage,s effective bacterial clearance and reduction of inflammation. Conclusions: This study highlights the therapeutic potential of a novel phage vB_AbaS_qsb1 against A.baumannii, especially amid rising antibiotic resistance. With its safety confirmed,vB_AbaS_qsb1 showed potent antibacterial activity both in vitro and in vivo, significantly reducing bacterial loads and improving survival in mouse models. This research also provides a valuable framework for the isolation, genomic analysis, and evaluation of A.baumannii phages.

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