Targeting Matrix Exopolysaccharides to Disrupt <em>Pseudomonas aeruginosa</em> Biofilms in Cystic Fibrosis

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.

Advances in Nanotechnology for Biofilm Inhibition

“…Biofilm formation in P. aeruginosa is highly regulated and a complex process that involves multiple molecular interactions . It typically begins with the attachment of individual P. aeruginosa cells, followed by the microcolony formation and the EPS matrix synthesis . The EPS matrix is composed of polysaccharides, such as alginate, and proteins, such as extracellular DNA and exopolysaccharides .…”

“… 60 It typically begins with the attachment of individual P. aeruginosa cells, followed by the microcolony formation and the EPS matrix synthesis. 61 The EPS matrix is composed of polysaccharides, such as alginate, and proteins, such as extracellular DNA and exopolysaccharides. 62 According to a number of studies, polysaccharide intercellular antigen (PIA) is responsible for biofilm development, though there is additional evidence that S. aureus can form biofilms irrespective of PIA.…”

Light-Based Anti-Biofilm and Antibacterial Strategies

“…In general, the combination of EPS synthesis inhibitors or EPS-degrading enzymes, which lack intrinsic antibacterial activity, with antimicrobial agents could be a good option for biofilm removal [ 187 ]. Many reviews on EPS degradation and synthesis inhibition have discussed this strategy in detail [ 188 , 189 ].…”