Genomic variation in Pseudomonas aeruginosa clinical respiratory isolates with de novo resistance to a bacteriophage cocktail

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dc.contributor.authorFong, S.A.
dc.contributor.authorBouras, G.
dc.contributor.authorHoutak, G.
dc.contributor.authorNepal, R.
dc.contributor.authorFeizi, S.
dc.contributor.authorMorales, S.
dc.contributor.authorPsaltis, A.J.
dc.contributor.authorWormald, P.-J.
dc.contributor.authorVreugde, S.
dc.contributor.editorVan Tyne, D.
dc.date.issued2025
dc.description.abstractPseudomonas aeruginosa is an opportunistic pathogen that can cause sinus infections and pneumonia in cystic fibrosis (CF) patients. Bacteriophage therapy is being investigated as a treatment for antibiotic-resistant P. aeruginosa infections. Although virulent bacteriophages have shown promise in treating P. aeruginosa infections, the development of bacteriophage-insensitive mutants (BIMs) in the presence of bacteriophages has been described. The aim of this study was to examine the genetic changes associated with the BIM phenotype. Biofilms of three genetically distinct P. aeruginosa strains, including PAO1 (ATCC 15692), and two clinical respiratory isolates (one CF and one non-CF) were grown for 7 days and treated with either a cocktail of four bacteriophages or a vehicle control for 7 consecutive days. BIMs isolated from the biofilms were detected by streak assays, and resistance to the phage cocktail was confirmed using spot test assays. Comparison of whole genome sequencing between the recovered BIMs and their respective vehicle control-treated phage-sensitive isolates revealed structural variants in two strains, and several small variants in all three strains. These variations involved a TonB-dependent outer membrane receptor in one strain, and mutations in lipopolysaccharide synthesis genes in two strains. Prophage deletion and induction were also noted in two strains, as well as mutations in several genes associated with virulence factors. Mutations in genes involved in susceptibility to conventional antibiotics were also identified in BIMs, with both decreased and increased antibiotic sensitivity to various antibiotics being observed. These findings may have implications for future applications of lytic phage therapy.
dc.description.statementofresponsibilityStephanie A. Fong, George Bouras, Ghais Houtak, Roshan Nepal, Sholeh Feizi, Sandra Morales, Alkis J. Psaltis, Peter-John Wormald, Sarah Vreugde
dc.identifier.citationMicrobiology Spectrum, 2025; 13(5):e02149-24-1-e02149-24-22
dc.identifier.doi10.1128/spectrum.02149-24
dc.identifier.issn2165-0497
dc.identifier.issn2165-0497
dc.identifier.orcidBouras, G. [0000-0002-5885-4186]
dc.identifier.orcidFeizi, S. [0000-0001-5489-4650]
dc.identifier.orcidPsaltis, A.J. [0000-0003-2197-0797] [0000-0003-2967-1855]
dc.identifier.orcidWormald, P.-J. [0000-0001-7753-7277]
dc.identifier.orcidVreugde, S. [0000-0003-4719-9785]
dc.identifier.urihttps://hdl.handle.net/2440/146308
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.relation.grantNHMRC
dc.rights© 2025 Fong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
dc.source.urihttps://doi.org/10.1128/spectrum.02149-24
dc.subjectbacteriophage
dc.subjectcystic fibrosis
dc.subjectmultidrug resistance
dc.subjectPseudomonas aeruginosa
dc.subject.meshBiofilms
dc.subject.meshPseudomonas Phages
dc.subject.meshPseudomonas Infections
dc.subject.meshAnti-Bacterial Agents
dc.subject.meshMutation
dc.subject.meshGenome, Bacterial
dc.subject.meshGenetic Variation
dc.subject.meshPhage Therapy
dc.subject.meshWhole Genome Sequencing
dc.titleGenomic variation in Pseudomonas aeruginosa clinical respiratory isolates with de novo resistance to a bacteriophage cocktail
dc.typeJournal article
pubs.publication-statusPublished

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