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Pf bacteriophages hinder sputum antibiotic diffusion via electrostatic binding.

Qingquan Chen1, Pam Cai2, Tony Hong Wei Chang1

  • 1Division of Infectious Diseases and Geographic Medicine, Dept. of Medicine, Stanford University School of Medicine, Beckman Center, 279 Campus Drive, Stanford, CA 94305, USA.

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Chronic Pseudomonas aeruginosa (Pa) infections in cystic fibrosis patients are worsened by the phage Pf, which hinders antibiotic diffusion. This study reveals how Pf and sputum polymers impede drug delivery, offering insights for new treatments.

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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.