Pf bacteriophages hinder sputum antibiotic diffusion via electrostatic binding

Qingquan Chen, Pam Cai, Tony Hong Wei Chang, Elizabeth Burgener, Michael J. Kratochvil, Aditi Gupta, Aviv Hargill, Patrick R. Secor, Josefine Eilsø Nielsen, Annelise E. Barron, Carlos Milla, Sarah C. Heilshorn, Andy Spakowitz, Paul L. Bollyky

Research output: Contribution to journalArticlepeer-review

Abstract

Despite great progress in the field, chronic Pseudomonas aeruginosa (Pa) infections remain a major cause of mortality in patients with cystic fibrosis (pwCF), necessitating treatment with antibiotics. Pf is a filamentous bacteriophage produced by Pa and acts as a structural element in Pa biofilms. Pf presence has been associated with antibiotic resistance and poor outcomes in pwCF, although the underlying mechanisms are unclear. We have investigated how Pf and sputum biopolymers impede antibiotic diffusion using pwCF sputum and fluorescent recovery after photobleaching. We demonstrate that tobramycin interacts with Pf and sputum polymers through electrostatic interactions. We also developed a set of mathematical models to analyze the complex observations. Our analysis suggests that Pf in sputum reduces the diffusion of charged antibiotics due to a greater binding constant associated with organized liquid crystalline structures formed between Pf and sputum polymers. This study provides insights into antibiotic tolerance mechanisms in chronic Pa infections and may offer potential strategies for novel therapeutic approaches.

Original languageEnglish
Article numbereadl5576
Pages (from-to)eadl5576
JournalScience advances
Volume10
Issue number22
DOIs
StatePublished - May 2024

Keywords

  • Anti-Bacterial Agents/pharmacology
  • Bacteriophages
  • Biofilms/drug effects
  • Cystic Fibrosis/metabolism
  • Diffusion
  • Humans
  • Pseudomonas Infections/drug therapy
  • Pseudomonas aeruginosa/drug effects
  • Sputum/microbiology
  • Static Electricity
  • Tobramycin/pharmacology

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