Anti-Psl Targeting of Pseudomonas aeruginosa Biofilms for Neutrophil-Mediated Disruption

Area of Science:

• Microbiology and Immunology
• Infectious Diseases
• Biotechnology

Background:

• Bacterial biofilms are a significant challenge in treating persistent infections due to their resistance to antibiotics.
• Antibody-based therapies offer a novel approach to target specific biofilm components for enhanced bacterial clearance.
• Previous studies showed anti-Psl monoclonal antibodies (mAbs) are effective against planktonic Pseudomonas aeruginosa but their efficacy against biofilms is unknown.

Purpose of the Study:

• To investigate the activity of anti-Psl mAbs against mature Pseudomonas aeruginosa biofilms.
• To evaluate the potential of anti-Psl mAbs as an adjunctive therapy with neutrophils and antibiotics for biofilm infections.

Main Methods:

• Assessed binding of anti-Psl mAbs to Psl exopolysaccharide in mature in vitro biofilms and chronic infection models.
• Evaluated the ability of mAbs to inhibit early biofilm formation and reduce mature biofilm biomass in the presence of neutrophils.
• Tested the combined efficacy of mAb mixtures, neutrophils, and meropenem antibiotic against P. aeruginosa biofilms.

Main Results:

• Anti-Psl mAbs demonstrated stratified binding within mature biofilms and recognized Psl in chronic infection contexts.
• mAbs showed differential inhibition of early biofilm development and biomass reduction with neutrophils.
• A combination of mAbs and neutrophils achieved significant biomass reduction, further enhanced by meropenem; bacterial killing correlated with mAb epitope binding.

Conclusions:

• Anti-Psl mAbs exhibit potential for targeting P. aeruginosa biofilms.
• These mAbs may serve as promising adjunctive agents, enhancing antibiotic efficacy for treating chronic biofilm infections.
• The findings support further development of antibody-based strategies to combat recalcitrant biofilm infections.