Inhaled bacteriophage-loaded polymeric microparticles ameliorate acute lung infections
Inhaled bacteriophage-loaded polymeric microparticles ameliorate acute lung infections
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DOI：
10.1038/s41551-018-0263-5
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发表时间：
2018-11-01
影响因子：
28.1
通讯作者：
Garcia, Andres J.
中科院分区：
文献类型：
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作者：
Agarwal, Rachit;Johnson, Christopher T.;Garcia, Andres J.
与肺炎相关的肺部感染，或由铜绿假单胞菌或其他细菌引起的囊性纤维化，导致显著的发病率和死亡率，部分原因是多药耐药性的发展，也是对最后手段抗生素的耐药性。裂解性噬菌体（即专门杀死细菌的病毒）可以减少肺部相关感染，但它们的临床应用受到难以将活性噬菌体输送到肺部深处的阻碍。在这里，我们表明，噬菌体负载的聚合物微粒存款通过干粉吸入整个肺，他们提供了积极的治疗。负载噬菌体的微粒有效地减少了野生型和囊性纤维化跨膜传导调节因子敲除小鼠中的铜绿假单胞菌感染和相关炎症，并将小鼠从肺炎相关死亡中拯救出来。这些聚合物微粒可能构成用于根除医院获得性肺部感染和与囊性纤维化相关的感染的临床上可转化的疗法。
Lung infections associated with pneumonia, or cystic fibrosis caused by Pseudomonas aeruginosa or other bacteria, result in significant morbidity and mortality, in part owing to the development of multidrug resistance, also against last-resort antibiotics. Lytic bacteriophages (that is, viruses that specifically kill bacteria) can reduce lung-associated infections, yet their clinical use is hindered by difficulties in delivering active phages to the deep lung. Here, we show that phage-loaded polymeric microparticles deposit throughout the lung via dry powder inhalation and that they deliver active phages. Phage-loaded microparticles effectively reduced P. aeruginosa infections and the associated inflammation in wild-type and cystic fibrosis trans-membrane-conductance-regulator knockout mice, and rescued the mice from pneumonia-associated death. These polymeric microparticles might constitute a clinically translatable therapy for eradicating hospital-acquired lung infections and infections associated with cystic fibrosis.