Correlation of Pseudomonas aeruginosa Phage Resistance with the Numbers and Types of Antiphage Systems
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Published:2024-01-24
Issue:3
Volume:25
Page:1424
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Burke Kevin A.1, Urick Caitlin D.1ORCID, Mzhavia Nino1, Nikolich Mikeljon P.1ORCID, Filippov Andrey A.1ORCID
Affiliation:
1. Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Abstract
Phage therapeutics offer a potentially powerful approach for combating multidrug-resistant bacterial infections. However, to be effective, phage therapy must overcome existing and developing phage resistance. While phage cocktails can reduce this risk by targeting multiple receptors in a single therapeutic, bacteria have mechanisms of resistance beyond receptor modification. A rapidly growing body of knowledge describes a broad and varied arsenal of antiphage systems encoded by bacteria to counter phage infection. We sought to understand the types and frequencies of antiphage systems present in a highly diverse panel of Pseudomonas aeruginosa clinical isolates utilized to characterize novel antibacterials. Using the web-server tool PADLOC (prokaryotic antiviral defense locator), putative antiphage systems were identified in these P. aeruginosa clinical isolates based on sequence homology to a validated and curated catalog of known defense systems. Coupling this host bacterium sequence analysis with host range data for 70 phages, we observed a correlation between existing phage resistance and the presence of higher numbers of antiphage systems in bacterial genomes. We were also able to identify antiphage systems that were more prevalent in highly phage-resistant P. aeruginosa strains, suggesting their importance in conferring resistance.
Funder
Congressionally Directed Medical Research Programs, Peer Reviewed Medical Research Program Military Infectious Diseases Research Program
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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