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

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

doi:10.1128/msphere.01216-20

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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

, Julian Forton, Eshwar Mahenthiralingam

, Philip D. Rye, Katja E. Hill

, David W. Thomas, Manon F. Pritchard

mSphere, Volume: 6, Issue: 1

Swansea University Author: Lydia Powell

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DOI (Published version): 10.1128/msphere.01216-20

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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first_indexed	2022-11-09T12:58:18Z
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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. 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spelling	2022-11-09T13:00:15.4062814 v2 61612 2022-10-20 Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy 0e7e702952672bcbfdfd4974199202fb 0000-0002-8641-0160 Lydia Powell Lydia Powell true false 2022-10-20 BMS 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. Journal Article mSphere 6 1 American Society for Microbiology 2379-5042 cystic fibrosis, Pseudomonas aeruginosa, alginate oligosaccharide, biofilm, bead model 20 1 2021 2021-01-20 10.1128/msphere.01216-20 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 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). 2022-11-09T13:00:15.4062814 2022-10-20T14:20:51.2866908 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Juliette L. Oakley 1 Rebecca Weiser 2 Lydia Powell 0000-0002-8641-0160 3 Julian Forton 4 Eshwar Mahenthiralingam 0000-0001-9014-3790 5 Philip D. Rye 6 Katja E. Hill 0000-0002-8590-0117 7 David W. Thomas 8 Manon F. Pritchard 0000-0002-5135-4744 9 61612__25713__f3a480f3cd314a269936b83cfe8b93fe.pdf 61612.pdf 2022-11-09T12:58:48.9835830 Output 2332931 application/pdf Version of Record true © 2021 Oakley et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license. true eng https://creativecommons.org/licenses/by/4.0/
title	Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy
spellingShingle	Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy Lydia Powell
title_short	Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy
title_full	Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy
title_fullStr	Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy
title_full_unstemmed	Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy
title_sort	Phenotypic and Genotypic Adaptations in Pseudomonas aeruginosa Biofilms following Long-Term Exposure to an Alginate Oligomer Therapy
author_id_str_mv	0e7e702952672bcbfdfd4974199202fb
author_id_fullname_str_mv	0e7e702952672bcbfdfd4974199202fb_***_Lydia Powell
author	Lydia Powell
author2	Juliette L. Oakley Rebecca Weiser Lydia Powell Julian Forton Eshwar Mahenthiralingam Philip D. Rye Katja E. Hill David W. Thomas Manon F. Pritchard
format	Journal article
container_title	mSphere
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container_issue	1
publishDate	2021
institution	Swansea University
issn	2379-5042
doi_str_mv	10.1128/msphere.01216-20
publisher	American Society for Microbiology
college_str	Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
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department_str	Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description	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.
published_date	2021-01-20T04:20:33Z
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score	11.013148

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

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