Polyguluronate simulations shed light onto the therapeutic action of OligoG CF-5/20

Abstract

Chronic mucoid P. aeruginosa cystic fibrosis (CF) lung infections are associated with the development of a biofilm composed of anionic acetylated exopolysaccharide (EPS) alginate, electrostatically stabilised by extracellular Ca²⁺ ions. OligoG CF-5/20, a low molecular weight guluronate rich oligomer, is emerging as a novel therapeutic capable of disrupting mature P. aeruginosa biofilms. However, its method of therapeutic action on the mucoid biofilm EPS is not definitively known at a molecular level. This work, utilising molecular dynamics (MD) and Density-Functional Theory (DFT), has revealed that OligoG CF-5/20 interaction with the EPS is facilitated solely through bridging Ca²⁺ ions, which are not liberated from their native EPS binding sites upon OligoG CF-5/20 dispersal, suggesting that OligoG CF-5/20 does not cause disruptions to mature P. aeruginosa biofilms through breaking EPS-Ca²⁺-EPS ionic cross-links. Rather it is likely that the therapeutic activity arises from sequestering free Ca²⁺ ions and preventing further Ca²⁺ induced EPS aggregation.

Keywords: Density-functional theory; Molecular dynamics; Mucoid biofilms; OligoG CF-5/20; P. aeruginosa.