Deciphering multivalent glycocluster-lectin interactions through AFM characterization of the self-assembled...

Area of Science:

• Microbiology
• Biochemistry
• Biophysics

Background:

• Pseudomonas aeruginosa is a major cause of lung infections, particularly in cystic fibrosis patients.
• The emergence of antibiotic-resistant strains and biofilm formation necessitates novel therapeutic strategies.
• LecA lectins are crucial virulence factors for P. aeruginosa, mediating bacterial adhesion to host cells via galactose binding.

Purpose of the Study:

• To investigate the interaction between P. aeruginosa LecA lectins and synthetic glycoclusters.
• To understand how glycocluster architecture influences binding affinity and arrangement with LecA.
• To explore the potential of glycoclusters as a therapeutic approach to inhibit bacterial adhesion.

Main Methods:

• Atomic force microscopy (AFM) imaging to visualize LecA-glycocluster arrangements.
• Molecular dynamics (MD) simulations to analyze the binding interactions at a molecular level.
• Synthesis and characterization of five distinct glycoclusters with varying core and branch structures.

Main Results:

• Glycocluster-LecA arrangements are highly dependent on the glycocluster's architecture.
• The core structure influences the geometric rigidity and branch directionality.
• Branch composition affects the compactness of the complex and the ease of binding, allowing for modulation of affinity.

Conclusions:

• Synthetic glycoclusters can effectively bind to P. aeruginosa LecA lectins.
• Tailoring glycocluster architecture offers a means to optimize affinity and binding characteristics.
• These findings support the development of glycocluster-based therapeutics to combat P. aeruginosa infections.