In vivo efficacy of phage cocktails against carbapenem resistance Acinetobacter baumannii in the rat pneumonia model

作者：Shibin Li, Bingdong Wei, Le Xu, Cong Cong, Bilal Murtaza, Lili Wang, Xiaoyu Li, Jibin Li, Mu Xu, Jiajun Yin, Yongping Xu · 发表于：Journal of Virology · 年份：2024 · DOI：10.1128/jvi.00467-24 · 被引用次数：16 · 研究领域：Bacteriophages and microbial interactions、Antibiotic Resistance in Bacteria、Vibrio bacteria research studies

ABSTRACT Acinetobacter baumannii , an opportunistic pathogen, poses a significant threat in intensive care units, leading to severe nosocomial infections. The rise of multi-drug-resistant strains, particularly carbapenem-resistant A. baumannii , has created formidable challenges for effective treatment. Given the prolonged development cycle and high costs associated with antibiotics, phages have garnered clinical attention as an alternative for combating infections caused by drug-resistant bacteria. However, the utilization of phage therapy encounters notable challenges, including the narrow host spectrum, where each phage targets a limited subset of bacteria, increasing the risk of phage resistance development. Additionally, uncertainties in immune system dynamics during treatment hinder tailoring symptomatic interventions based on patient-specific states. In this study, we isolated two A. baumannii phages from wastewater and conducted a comprehensive assessment of their potential applications. This evaluation included sequencing analysis, genome classification, pH and temperature stability assessments, and in vitro bacterial inhibition assays. Further investigations involved analyzing histological and cytokine alterations in rats undergoing phage cocktail treatment for pneumonia. The therapeutic efficacy of the phages was validated, and transcriptomic studies of rat lung tissue during phage treatment revealed crucial changes in the immune system. The findings from our study...