Pf bacteriophages hinder sputum antibiotic diffusion via electrostatic binding.
Qingquan ChenPam CaiTony Hong Wei ChangElizabeth BurgenerMichael J KratochvilAditi GuptaAviv HargilPatrick R SecorJosefine Eilsø NielsenAnnelise E BarronCarlos MillaSarah C HeilshornAndy SpakowitzPaul L BollykyPublished in: bioRxiv : the preprint server for biology (2024)
Despite great progress in the field, chronic Pseudomonas aeruginosa ( Pa ) infections remain a major cause of morbidity and mortality in patients with cystic fibrosis, necessitating treatment with inhaled antibiotics. Pf phage is a filamentous bacteriophage produced by Pa that has been reported to act as a structural element in Pa biofilms. Pf presence has been associated with resistance to antibiotics and poor outcomes in cystic fibrosis, though the underlying mechanisms are unclear. Here, we have investigated how Pf phages and sputum biopolymers impede antibiotic diffusion using human sputum samples and fluorescent recovery after photobleaching. We demonstrate that tobramycin interacts with Pf phages and sputum polymers through electrostatic interactions. We also developed a set of mathematical models to analyze the complex observations. Our analysis suggests that Pf phages in sputum reduce the diffusion of charged antibiotics due to a greater binding constant associated with organized liquid crystalline structures formed between Pf phages and sputum polymers. This study provides insights into antibiotic tolerance mechanisms in chronic Pa infections and may offer potential strategies for novel therapeutic approaches.
Keyphrases
- cystic fibrosis
- pseudomonas aeruginosa
- lung function
- pulmonary tuberculosis
- mycobacterium tuberculosis
- biofilm formation
- end stage renal disease
- acinetobacter baumannii
- endothelial cells
- ejection fraction
- chronic kidney disease
- newly diagnosed
- type diabetes
- molecular dynamics simulations
- risk assessment
- escherichia coli
- ionic liquid
- dna binding
- transcription factor
- mass spectrometry
- patient reported outcomes
- human health
- insulin resistance
- replacement therapy