Abstract
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 β-D-mannuronate (M) and β-D-mannuronate-α-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.
Highlights
Bacterial biofilms consist of a community of bacteria embedded in an extracellular matrix (ECM) of polysaccharide
The ECM limits the penetration of antimicrobials, which contributes to the minimum inhibitory concentrations of antimicrobials against biofilms being 100-1000-fold higher than those required for treating planktonic bacteria [2]
The relationship between structural chemistry and bacterial virulence has been probed in detail for mucoid P. aeruginosa extracellular polysaccharide molecular systems
Summary
Bacterial biofilms consist of a community of bacteria embedded in an extracellular matrix (ECM) of polysaccharide. There was a high correlation coefficient between calcium and magnesium in the CF sputum samples [21] These ions serve to create permanent electrostatic cross-links in the extracellular polysaccharide (EPS), established between neighbouring M-M and M-G junctions [25], further stabilizing the ECM [26]. A more recent study examining the structure and reactivity of the M-M, G-G, M-G and G-M conformations, showed that the stability, as defined by the hardness (η), of the cation-disaccharide complexes decreased from magnesium to calcium to sodium, a trend inversely proportional to the ionic radius [39] This suggests that magnesium-cross-linked alginate chains are more stable than those cross-linked with calcium. The models predict the potent cross-linking ability of the ions relative to one another and indicate that stable cation complexation results from a combination of electrostatic and steric factors
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