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A low molecular weight alginate oligosaccharide disrupts pseudomonal microcolony formation and enhances antibiotic effectiveness

Pritchard, Manon, Powell, Lydia, Jack, Alison, Powell, Kate, Beck, Konrad, Florance, Hannah, Forton, Julian, Rye, Phil, Dessen, Arne, Hill, Katja E. and Thomas, David W 2017. A low molecular weight alginate oligosaccharide disrupts pseudomonal microcolony formation and enhances antibiotic effectiveness. Antimicrobial Agents and Chemotherapy 61 (9) , e00762-17. 10.1128/AAC.00762-17

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Abstract

In chronic respiratory disease the formation of dense, 3-dimensional ‘micro colonies' by Pseudomonas aeruginosa within the airway plays an important role in contributing to resistance to treatment. An in vitro biofilm model of pseudomonal microcolony formation using artificial sputum (AS) medium was established to study the effects of low molecular weight alginate oligomers (OligoG CF-5/20) on pseudomonal growth, microcolony formation and the efficacy of colistin. The studies employed clinical cystic fibrosis (CF) isolates (n=3) and reference non-mucoid and mucoid multi-drug resistant (MDR) CF isolates (n=7). Bacterial growth, biofilm development and disruption were studied using cell-viability assays and image analysis using scanning electron- and confocal laser scanning microscopy. Pseudomonal growth in AS medium was associated with increased ATP production (p<0.05) and the formation (at 48 h) of discrete (>10 μm) microcolonies. In conventional growth medium, colistin retained an ability to inhibit growth of planktonic bacteria, although the MIC was increased (0.1 to 0.4 μg/ml) in AS medium versus. In contrast, in an established biofilm model in the AS medium, the efficacy of colistin was decreased. OligoG CF-5/20 (≥2%) treatment however, induced dose-dependent biofilm disruption (p<0.05), and led to colistin retaining its antimicrobial activity (p<0.05). Whilst circular dichroism indicated that OligoG CF-5/20 did not change the orientation of the alginate carboxyl groups, mass-spectrometry demonstrated that the oligomers induced dose-dependent (>0.2%; p<0.05) reductions in pseudomonal quorum sensing signaling. These findings reinforce the potential clinical significance of microcolony formation in the CF lung, and highlight a novel approach to treat MDR pseudomonal infections.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: R Medicine > RK Dentistry
Publisher: American Society for Microbiology
ISSN: 0066-4804
Funders: Norwegian Research Council
Date of First Compliant Deposit: 13 September 2017
Date of Acceptance: 6 June 2017
Last Modified: 18 Oct 2019 22:44
URI: http://orca.cf.ac.uk/id/eprint/101264

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