Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Targeting Matrix Exopolysaccharides to Disrupt Pseudomonas aeruginosa Biofilms in Cystic Fibrosis

Version 1 : Received: 31 January 2023 / Approved: 2 February 2023 / Online: 2 February 2023 (09:38:31 CET)

How to cite: Chung, J.; Eisha, S.; Park, S.; Morris, A.; Martin, I. Targeting Matrix Exopolysaccharides to Disrupt Pseudomonas aeruginosa Biofilms in Cystic Fibrosis. Preprints 2023, 2023020042. https://doi.org/10.20944/preprints202302.0042.v1 Chung, J.; Eisha, S.; Park, S.; Morris, A.; Martin, I. Targeting Matrix Exopolysaccharides to Disrupt Pseudomonas aeruginosa Biofilms in Cystic Fibrosis. Preprints 2023, 2023020042. https://doi.org/10.20944/preprints202302.0042.v1

Abstract

In cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a cause of increased morbidity and mortality, especially in patients for whom infection becomes chronic and there is reliance on long-term suppressive therapies. Current antimicrobials, though varied mechanistically and by mode of delivery, are inadequate not only due to eradication failure in many cases, but also because they do not halt the progression of lung function decline over time. One of the reasons for this failure is thought to be the biofilm mode of growth of P. aeruginosa, wherein self-secreted exopolysaccharides (EPSs) provide physical protection against antibiotics and an array of niches with resulting metabolic and phenotypic heterogeneity. Targeting the three EPSs secreted by P. aeruginosa (alginate, Psl and Pel) is currently under investigation as a way of disrupting the biofilm extracellular matrix to potentiate the action of antibiotics. In this review, we look at each EPS as a potential therapeutic target for combatting pulmonary infection with P. aeruginosa in CF, with a particular focus on the current evidence for these emerging therapies and barriers to bringing these therapies into clinic.

Keywords

Cystic fibrosis; Pseudomonas aeruginosa; antibiotic adjunct; anti-biofilm; biofilm-degrading enzymes; matrix exopolysaccharides; alginate oligosaccharide

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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