Cation complexation by mucoid Pseudomonas aeruginosa extracellular polysaccharide

Mucoid Pseudomonas aeruginosa is a prevalent cystic fibrosis (CF) lung colonizer, producing an extracellular matrix (ECM) composed predominantly of the extracellular polysaccharide (EPS) alginate. The ECM limits antimicrobial penetration and, consequently, CF sufferers are prone to chronic mucoid P. aeruginosa lung infections. Interactions between cations with elevated concentrations in the CF lung and the anionic EPS, enhance the structural rigidity of the biofilm and exacerbates virulence. In this work, two large mucoid P. aeruginosa EPS models, based on beta -D-mannuronate (M) and beta -D-mannuronate-alpha -L-guluronate systems (M-G), and encompassing thermodynamically stable acetylation configurations-a structural motif unique to mucoid P. aeruginosa-were created. Using highly accurate first principles calculations, stable coordination environments adopted by the cations have been identified and thermodynamic stability quantified. These models show the weak cross-linking capability of Na+ and Mg2+ ions relative to Ca2+ ions and indicate a preference for cation binding within M-G blocks due to the smaller torsional rearrangements needed to reveal stable binding sites. The geometry of the chelation site influences the stability of the resulting complexes more than electrostatic interactions, and the results show nuanced chemical insight into previous experimental observations.

Automated summary

The study creates two large mucoid P. aeruginosa EPS models based on beta-D-mannuronate and beta-D-mannuronate-alpha-L-guluronate systems, encompassing thermodynamically stable acetylation configurations unique to mucoid P. aeruginosa. Using first principles calculations, the study identifies stable coordination environments of cations in CF lungs and quantifies their thermodynamic stability. The models demonstrate the weaker cross-linking capability of Na+ and Mg2+ ions compared to Ca2+ ions, with a preference for cation binding within M-G blocks due to smaller torsional rearrangements required to reveal stable binding sites. The geometry of chelation site influences the stability of resulting complexes more than electrostatic interactions, providing nuanced chemical insight into previous experimental observations.