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Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy

Juliette L. Oakley, Rebecca Weiser, Lydia Powell Orcid Logo, Julian Forton, Eshwar Mahenthiralingam Orcid Logo, Philip D. Rye, Katja E. Hill Orcid Logo, David W. Thomas, Manon F. Pritchard Orcid Logo

mSphere, Volume: 6, Issue: 1

Swansea University Author: Lydia Powell Orcid Logo

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Abstract

Chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) evolve to generate environmentally adapted biofilm communities, leading to increased patient morbidity and mortality. OligoG CF-5/20, a low-molecular-weight inhaled alginate oligomer therapy, is currently in phase IIb/III clinica...

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Published in: mSphere
ISSN: 2379-5042
Published: American Society for Microbiology 2021
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa61612
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Abstract: Chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) evolve to generate environmentally adapted biofilm communities, leading to increased patient morbidity and mortality. OligoG CF-5/20, a low-molecular-weight inhaled alginate oligomer therapy, is currently in phase IIb/III clinical trials in CF patients. Experimental evolution of P. aeruginosa in response to OligoG CF-5/20 was assessed using a bead biofilm model allowing continuous passage (45 days; ∼245 generations). Mutants isolated after OligoG CF-5/20 treatment typically had a reduced biofilm-forming ability and altered motility profile. Genotypically, OligoG CF-5/20 provided no selective pressure on genomic mutations within morphotypes. Chronic exposure to azithromycin, a commonly prescribed antibiotic in CF patients, with or without OligoG CF-5/20 in the biofilm evolution model also had no effect on rates of resistance acquisition. Interestingly, however, cross-resistance to other antibiotics (e.g., aztreonam) was reduced in the presence of OligoG CF-5/20. Collectively, these findings show no apparent adverse effects from long-term exposure to OligoG CF-5/20, instead resulting in both fewer colonies with multidrug resistance (MDR)-associated phenotypes and improved antibiotic susceptibility of P. aeruginosa.
Keywords: cystic fibrosis, Pseudomonas aeruginosa, alginate oligosaccharide, biofilm, bead model
College: Faculty of Medicine, Health and Life Sciences
Funders: This study was supported by the Research Council of Norway (245598 and 228542/O30), AlgiPharma AS, Sandvika, Norway, and the European Social Fund (Ser Cymru II; TG/JV/VSM1236053). Genome resequencing was supported by funds from the UK Medical Research Council’s Proximity to Discovery scheme at Cardiff University (513400) and the Wellcome Trust Institutional Strategic Support Fund award held at Cardiff University (513087).
Issue: 1