Pseudomonas aeruginosa Biofilm Eradication via Nitric Oxide-Releasing Cyclodextrins

Area of Science:

• Microbiology
• Biomedical Engineering
• Drug Discovery

Background:

• Pseudomonas aeruginosa is a primary cause of morbidity and mortality in cystic fibrosis (CF) patients.
• Chronic P. aeruginosa infections in CF are difficult to eradicate due to protective mucus and biofilm matrices.
• Biofilm matrix composition influences viscoelastic properties and antibiotic efficacy.

Purpose of the Study:

• To investigate the impact of a CF-like environment on P. aeruginosa biofilm susceptibility to nitric oxide (NO).
• To compare the efficacy of NO-releasing agents with conventional antibiotics against P. aeruginosa biofilms.

Main Methods:

• Utilized parallel plate macrorheology and particle tracking microrheology to assess biofilm properties.
• Grew P. aeruginosa biofilms in a CF-like medium (containing mucins and DNA) and a standard medium (tryptic soy broth).
• Evaluated biofilm susceptibility to NO-releasing cyclodextrins and conventional antibiotics (tobramycin, colistin).

Main Results:

• CF-like biofilms had higher DNA concentrations and increased viscoelastic moduli compared to standard biofilms.
• Increased viscoelasticity correlated with enhanced tolerance to tobramycin and colistin.
• NO-releasing cyclodextrins eradicated all tested P. aeruginosa biofilms at a consistent concentration, regardless of matrix composition.

Conclusions:

• Biofilm matrix composition significantly affects P. aeruginosa viscoelasticity and antibiotic tolerance in CF.
• Nitric oxide demonstrates potent antibiofilm activity against P. aeruginosa, overcoming matrix-induced tolerance.
• NO-based therapies represent a promising alternative to conventional antibiotics for treating P. aeruginosa biofilm infections in CF.