Cation complexation by mucoid Pseudomonas aeruginosa extracellular polysaccharide

Area of Science:

• Biochemistry
• Microbiology
• Computational Chemistry

Background:

• Mucoid Pseudomonas aeruginosa is a common lung colonizer in cystic fibrosis (CF) patients.
• The bacterium produces an extracellular matrix (ECM) rich in alginate, hindering antimicrobial penetration and promoting chronic infections.
• Cation interactions with the anionic alginate ECM enhance biofilm rigidity and virulence in the CF lung environment.

Purpose of the Study:

• To create computational models of mucoid Pseudomonas aeruginosa extracellular polysaccharide (EPS) structures.
• To investigate cation coordination environments and quantify the thermodynamic stability of these interactions.
• To elucidate the role of specific cations in modulating biofilm structure and virulence.

Main Methods:

• Development of two large mucoid P. aeruginosa EPS models (M and M-G systems) with stable acetylation configurations.
• Application of first-principles calculations to identify stable cation coordination sites.
• Quantification of thermodynamic stability and analysis of cation binding preferences.

Main Results:

• Identified stable coordination environments for cations interacting with the EPS models.
• Demonstrated weaker cross-linking capabilities of Na+ and Mg2+ compared to Ca2+ ions.
• Revealed a preference for cation binding within M-G blocks due to favorable torsional rearrangements.
• Showed that chelation site geometry significantly impacts complex stability over electrostatic interactions.

Conclusions:

• Cation binding geometry is a critical determinant of biofilm stability and P. aeruginosa virulence in CF lungs.
• Calcium ions play a more significant role in reinforcing the alginate biofilm structure than sodium or magnesium ions.
• The study provides detailed chemical insights into experimental observations of cation-EPS interactions in CF.