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

Oakley, Juliette L., Weiser, Rebecca ORCID: https://orcid.org/0000-0003-3983-3272, Powell, Lydia C. ORCID: https://orcid.org/0000-0002-8641-0160, Forton, Julian ORCID: https://orcid.org/0000-0002-0580-0432, Mahenthiralingam, Eshwar ORCID: https://orcid.org/0000-0001-9014-3790, Rye, Philip D., Hill, Katja E. ORCID: https://orcid.org/0000-0002-8590-0117, Thomas, David W. ORCID: https://orcid.org/0000-0001-7319-5820 and Pritchard, Manon F. ORCID: https://orcid.org/0000-0002-5135-4744 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:	25 Feb 2024 13:59
URI:	https://orca.cardiff.ac.uk/id/eprint/137822

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