Nordstrom Hayley R, Evans Daniel R, Finney Amanda G, Westbrook Kevin J, Zamora Paula F, Hofstaedter Casey E, Yassin Mohamed H, Pradhan Akansha, Iovleva Alina, Ernst Robert K, Bomberger Jennifer M, Shields Ryan K, Doi Yohei, Van Tyne Daria
Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
iScience. 2022 May 10;25(6):104372. doi: 10.1016/j.isci.2022.104372. eCollection 2022 Jun 17.
infections can be difficult to treat and new therapeutics are needed. Bacteriophage therapy is a promising alternative to traditional antibiotics, but large numbers of isolated and characterized phages are lacking. We collected 23 diverse . isolates from people with cystic fibrosis (CF) and clinical infections, and used them to screen and isolate over a dozen . -targeting phages from hospital wastewater. Phages were characterized with genome sequencing, comparative genomics, and lytic activity screening against all 23 bacterial host isolates. We evolved bacterial mutants that were resistant to phage infection for four different phages, and used genome sequencing and functional analysis to study them further. We also tested phages for their ability to kill . grown in biofilms and on CF airway epithelial cells. Overall, this study demonstrates how systematic genomic and phenotypic characterization can be deployed to develop bacteriophages as precision antibiotics.
感染可能难以治疗，因此需要新的治疗方法。噬菌体疗法是传统抗生素的一种有前景的替代方法，但缺乏大量分离和表征的噬菌体。我们从囊性纤维化（CF）患者和临床感染患者中收集了23种不同的分离株，并利用它们从医院废水中筛选和分离出十几种靶向噬菌体。通过基因组测序、比较基因组学以及针对所有23种细菌宿主分离株的裂解活性筛选对噬菌体进行了表征。我们培育出了对四种不同噬菌体感染具有抗性的细菌突变体，并利用基因组测序和功能分析对它们进行了进一步研究。我们还测试了噬菌体杀死在生物膜中以及CF气道上皮细胞上生长的细菌的能力。总体而言，这项研究展示了如何通过系统的基因组和表型表征来开发噬菌体作为精准抗生素。
