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

Powell, Lydia C. ORCID: https://orcid.org/0000-0002-8641-0160, Pritchard, Manon F. ORCID: https://orcid.org/0000-0002-5135-4744, Ferguson, Elaine L. ORCID: https://orcid.org/0000-0002-0125-0234, Powell, Kate A. ORCID: https://orcid.org/0000-0002-8641-0160, Patel, Shree U., Rye, Phil D., Sakellakou, Stavroula-Melina, Buurma, Niklaas J. ORCID: https://orcid.org/0000-0003-0260-5057, Brilliant, Charles D., Copping, Jack M., Menzies, Georgina E. ORCID: https://orcid.org/0000-0002-6600-6507, Lewis, Paul D., Hill, Katja E. ORCID: https://orcid.org/0000-0002-8590-0117 and Thomas, David W. ORCID: https://orcid.org/0000-0001-7319-5820 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
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Nature Publishing Group
ISSN:	2055-5008
Date of First Compliant Deposit:	18 April 2018
Date of Acceptance:	6 June 2018
Last Modified:	22 Oct 2023 10:32
URI:	https://orca.cardiff.ac.uk/id/eprint/110780

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