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Targeted disruption of the extracellular polymeric network of pseudomonas aeruginosa biofilms by alginate oligosaccharides

Powell, Lydia C., Pritchard, Manon F., Ferguson, Elaine L., Powell, Kate A., Patel, Shree U., Rye, Phil D., Sakellakou, Stavroula, Buurma, Niklaas J., Brilliant, Charles D., Copping, Jack M., Menzies, Georgina, Lewis, Paul D., Hill, Katja E. and Thomas, David 2018. Targeted disruption of the extracellular polymeric network of pseudomonas aeruginosa biofilms by alginate oligosaccharides. npj Biofilms and Microbiomes 4 , 13. 10.1038/s41522-018-0056-3

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Abstract

Acquisition of a mucoid phenotype by Pseudomonas sp. in the lungs of cystic fibrosis (CF) patients, with subsequent over-production of extracellular polymeric substance (EPS), plays an important role in mediating the persistence of multi-drug resistant (MDR) infections. The ability of a low molecular weight (Mn = 3200 g mol−1) alginate oligomer (OligoG CF-5/20) to modify biofilm structure of mucoid Pseudomonas aeruginosa (NH57388A) was studied in vitro using scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) with Texas Red (TxRd®)-labelled OligoG and EPS histochemical staining. Structural changes in treated biofilms were quantified using COMSTAT image-analysis software of CLSM z-stack images, and nanoparticle diffusion. Interactions between the oligomers, Ca2+ and DNA were studied using molecular dynamics (MD) simulations, Fourier transform infrared spectroscopy (FTIR) and isothermal titration calorimetry (ITC). Imaging demonstrated that OligoG treatment (≥0.5%) inhibited biofilm formation, revealing a significant reduction in both biomass and biofilm height (P < 0.05). TxRd®-labelled oligomers readily diffused into established (24 h) biofilms. OligoG treatment (≥2%) induced alterations in the EPS of established biofilms; significantly reducing the structural quantities of EPS polysaccharides, and extracellular (e)DNA (P < 0.05) with a corresponding increase in nanoparticle diffusion (P < 0.05) and antibiotic efficacy against established biofilms. ITC demonstrated an absence of rapid complex formation between DNA and OligoG and confirmed the interactions of OligoG with Ca2+ evident in FTIR and MD modelling. The ability of OligoG to diffuse into biofilms, potentiate antibiotic activity, disrupt DNA-Ca2+-DNA bridges and biofilm EPS matrix highlights its potential for the treatment of biofilm-related infections.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Chemistry
Publisher: Nature Publishing Group: Open Access Journals - Option C / Nature Publishing Group
ISSN: 2055-5008
Date of First Compliant Deposit: 18 April 2018
Date of Acceptance: 6 June 2018
Last Modified: 10 Jun 2019 11:25
URI: http://orca-mwe.cf.ac.uk/id/eprint/110780

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