Pf bacteriophages hinder sputum antibiotic diffusion via electrostatic binding

Area of Science:

• Microbiology
• Biophysics
• Pharmacology

Background:

• Chronic Pseudomonas aeruginosa (Pa) infections are a leading cause of mortality in cystic fibrosis patients.
• The bacteriophage Pf, a structural component of Pa biofilms, is linked to antibiotic resistance and poor outcomes in patients with cystic fibrosis (pwCF).
• Mechanisms underlying Pf's impact on antibiotic efficacy remain unclear.

Purpose of the Study:

• To investigate how Pf and sputum biopolymers affect antibiotic diffusion in pwCF.
• To elucidate the interaction mechanisms between antibiotics, Pf, and sputum components.
• To develop models for understanding antibiotic tolerance in chronic Pa infections.

Main Methods:

• Utilized fluorescent recovery after photobleaching (FRAP) assays with pwCF sputum.
• Studied the diffusion of tobramycin in the presence of Pf and sputum biopolymers.
• Developed mathematical models to analyze diffusion dynamics.

Main Results:

• Demonstrated electrostatic interactions between tobramycin, Pf, and sputum polymers.
• Observed reduced diffusion of charged antibiotics in sputum containing Pf.
• Identified organized liquid crystalline structures formed by Pf and sputum polymers as key to reduced diffusion.

Conclusions:

• Pf and sputum biopolymers significantly impede charged antibiotic diffusion in pwCF.
• Electrostatic interactions and liquid crystalline structures contribute to antibiotic tolerance.
• Findings provide insights into therapeutic strategies for chronic Pa infections in cystic fibrosis.