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Phenotypic and genotypic adaptations in Pseudomonas aeruginosa biofilms following long-term exposure to an alginate oligomer therapy

Oakley, Juliette L., Weiser, Rebecca, Powell, Lydia C., Forton, Julian, Mahenthiralingam, Eshwar, Rye, Philip D., Hill, Katja E., Thomas, David W. and Pritchard, Manon F. 2021. Phenotypic and genotypic adaptations in Pseudomonas aeruginosa biofilms following long-term exposure to an alginate oligomer therapy. mSphere 6 (1) , e01216-20. 10.1128/mSphere.01216-20

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Biosciences
Publisher: American Society for Microbiology
ISSN: 2379-5042
Funders: MRC, Wellcome Trust
Date of First Compliant Deposit: 21 January 2021
Date of Acceptance: 22 December 2020
Last Modified: 29 Jan 2021 14:28
URI: http://orca.cf.ac.uk/id/eprint/137822

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