Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, Liverpool, UK.
Division of Evolution & Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, UK.
Nat Commun. 2024 Feb 20;15(1):1547. doi: 10.1038/s41467-024-45785-z.
Pseudomonas aeruginosa is a major nosocomial pathogen that causes severe disease including sepsis. Carbapenem-resistant P. aeruginosa is recognised by the World Health Organisation as a priority 1 pathogen, with urgent need for new therapeutics. As such, there is renewed interest in using bacteriophages as a therapeutic. However, the dynamics of treating pan-resistant P. aeruginosa with phage in vivo are poorly understood. Using a pan-resistant P. aeruginosa in vivo infection model, phage therapy displays strong therapeutic potential, clearing infection from the blood, kidneys, and spleen. Remaining bacteria in the lungs and liver displays phage resistance due to limiting phage adsorption. Yet, resistance to phage results in re-sensitisation to a wide range of antibiotics. In this work, we use phage steering in vivo, pre-exposing a pan resistant P. aeruginosa infection with a phage cocktail to re-sensitise bacteria to antibiotics, clearing the infection from all organs.
铜绿假单胞菌是一种主要的医院病原体，可导致包括败血症在内的严重疾病。耐碳青霉烯类铜绿假单胞菌被世界卫生组织认定为优先 1 级病原体，迫切需要新的治疗方法。因此，人们重新对噬菌体作为治疗方法产生了兴趣。然而，用噬菌体体内治疗泛耐药铜绿假单胞菌的动力学仍知之甚少。使用泛耐药铜绿假单胞菌体内感染模型，噬菌体治疗显示出很强的治疗潜力，可从血液、肾脏和脾脏中清除感染。由于噬菌体吸附受到限制，肺部和肝脏中的残留细菌对噬菌体表现出耐药性。然而，对噬菌体的耐药性导致对广泛的抗生素重新敏感。在这项工作中，我们在体内使用噬菌体引导，用噬菌体鸡尾酒预先暴露泛耐药铜绿假单胞菌感染，使细菌重新对抗生素敏感，从而从所有器官清除感染。
