Pf bacteriophages hinder sputum antibiotic diffusion via electrostatic binding-Reference-Cited by-同舟云学术

Pf bacteriophages hinder sputum antibiotic diffusion via electrostatic binding

Published:2024-05-31 Issue:22 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Chen Qingquan¹^ORCID,Cai Pam²^ORCID,Chang Tony Hong Wei¹^ORCID,Burgener Elizabeth³⁴^ORCID,Kratochvil Michael J.¹⁵^ORCID,Gupta Aditi¹^ORCID,Hargill Aviv¹^ORCID,Secor Patrick R.⁶^ORCID,Nielsen Josefine Eilsø⁷⁸^ORCID,Barron Annelise E.⁷^ORCID,Milla Carlos³^ORCID,Heilshorn Sarah C.⁵^ORCID,Spakowitz Andy²⁵^ORCID,Bollyky Paul L.¹^ORCID

Affiliation:

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

2. Department of Chemical Engineering, Stanford University, Stanford, CA, 94305, USA.

3. Center for Excellence in Pulmonary Biology, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.

4. Children’s Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA.

5. Department of Materials Science and Engineering, Stanford University, 476 Lomita Mall, Stanford, CA 94305, USA.

6. Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.

7. Department of Bioengineering, School of Medicine & School of Engineering, Stanford University, Stanford, CA 94305, USA.

8. Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adl5576

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