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Genomic characterization of lytic bacteriophages targeting genetically diverse Pseudomonas aeruginosa clinical isolates.

Authors :
Nordstrom HR
Evans DR
Finney AG
Westbrook KJ
Zamora PF
Hofstaedter CE
Yassin MH
Pradhan A
Iovleva A
Ernst RK
Bomberger JM
Shields RK
Doi Y
Van Tyne D
Source :
IScience [iScience] 2022 May 10; Vol. 25 (6), pp. 104372. Date of Electronic Publication: 2022 May 10 (Print Publication: 2022).
Publication Year :
2022

Abstract

Pseudomonas aeruginosa 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 P . aeruginosa isolates from people with cystic fibrosis (CF) and clinical infections, and used them to screen and isolate over a dozen P . aeruginosa -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 P . aeruginosa grown in biofilms in vitro and ex vivo on CF airway epithelial cells. Overall, this study demonstrates how systematic genomic and phenotypic characterization can be deployed to develop bacteriophages as precision antibiotics.<br />Competing Interests: J.B. is a consultant for BiomX, Inc. The other authors declare no competing interests.<br /> (© 2022 The Author(s).)

Details

Language :
English
ISSN :
2589-0042
Volume :
25
Issue :
6
Database :
MEDLINE
Journal :
IScience
Publication Type :
Academic Journal
Accession number :
35620437
Full Text :
https://doi.org/10.1016/j.isci.2022.104372