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Poly-L-Lysine to Fight Antibiotic Resistances of Pseudomonas aeruginosa

Pseudomonas aeruginosa is a major hospital-associated pathogen that can cause severe infections, most notably in patients with cystic fibrosis (CF) or those hospitalized in intensive care units. Given its remarkable ability to resist antibiotics, P. aeruginosa eradication has grown more challenging....

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Autores principales: Cezard, Adeline, Fouquenet, Delphine, Vasseur, Virginie, Jeannot, Katy, Launay, Fabien, Si-Tahar, Mustapha, Hervé, Virginie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917869/
https://www.ncbi.nlm.nih.gov/pubmed/36769174
http://dx.doi.org/10.3390/ijms24032851
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author Cezard, Adeline
Fouquenet, Delphine
Vasseur, Virginie
Jeannot, Katy
Launay, Fabien
Si-Tahar, Mustapha
Hervé, Virginie
author_facet Cezard, Adeline
Fouquenet, Delphine
Vasseur, Virginie
Jeannot, Katy
Launay, Fabien
Si-Tahar, Mustapha
Hervé, Virginie
author_sort Cezard, Adeline
collection PubMed
description Pseudomonas aeruginosa is a major hospital-associated pathogen that can cause severe infections, most notably in patients with cystic fibrosis (CF) or those hospitalized in intensive care units. Given its remarkable ability to resist antibiotics, P. aeruginosa eradication has grown more challenging. Therefore, there is an urgent need to discover and develop new strategies that can counteract P. aeruginosa-resistant strains. Here, we evaluated the efficacy of poly-L-lysine (pLK) in combination with commonly used antibiotics as an alternative treatment option against P. aeruginosa. First, we demonstrated by scanning electron microscopy that pLK alters the integrity of the surface membrane of P. aeruginosa. We also showed using a fluorometry test that this results in an enhanced permeability of the bacteria membrane. Based on these data, we further evaluated the effect of the combinations of pLK with imipenem, ceftazidime, or aztreonam using the broth microdilution method in vitro. We found synergies in terms of bactericidal effects against either sensitive or resistant P. aeruginosa strains, with a reduction in bacterial growth (up to 5-log(10) compared to the control). Similarly, these synergistic and bactericidal effects were confirmed ex vivo using a 3D model of human primary bronchial epithelial cells maintained in an air–liquid interface. In conclusion, pLK could be an innovative antipseudomonal molecule, opening its application as an adjuvant antibiotherapy against drug-resistant P. aeruginosa strains.
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spelling pubmed-99178692023-02-11 Poly-L-Lysine to Fight Antibiotic Resistances of Pseudomonas aeruginosa Cezard, Adeline Fouquenet, Delphine Vasseur, Virginie Jeannot, Katy Launay, Fabien Si-Tahar, Mustapha Hervé, Virginie Int J Mol Sci Article Pseudomonas aeruginosa is a major hospital-associated pathogen that can cause severe infections, most notably in patients with cystic fibrosis (CF) or those hospitalized in intensive care units. Given its remarkable ability to resist antibiotics, P. aeruginosa eradication has grown more challenging. Therefore, there is an urgent need to discover and develop new strategies that can counteract P. aeruginosa-resistant strains. Here, we evaluated the efficacy of poly-L-lysine (pLK) in combination with commonly used antibiotics as an alternative treatment option against P. aeruginosa. First, we demonstrated by scanning electron microscopy that pLK alters the integrity of the surface membrane of P. aeruginosa. We also showed using a fluorometry test that this results in an enhanced permeability of the bacteria membrane. Based on these data, we further evaluated the effect of the combinations of pLK with imipenem, ceftazidime, or aztreonam using the broth microdilution method in vitro. We found synergies in terms of bactericidal effects against either sensitive or resistant P. aeruginosa strains, with a reduction in bacterial growth (up to 5-log(10) compared to the control). Similarly, these synergistic and bactericidal effects were confirmed ex vivo using a 3D model of human primary bronchial epithelial cells maintained in an air–liquid interface. In conclusion, pLK could be an innovative antipseudomonal molecule, opening its application as an adjuvant antibiotherapy against drug-resistant P. aeruginosa strains. MDPI 2023-02-02 /pmc/articles/PMC9917869/ /pubmed/36769174 http://dx.doi.org/10.3390/ijms24032851 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cezard, Adeline
Fouquenet, Delphine
Vasseur, Virginie
Jeannot, Katy
Launay, Fabien
Si-Tahar, Mustapha
Hervé, Virginie
Poly-L-Lysine to Fight Antibiotic Resistances of Pseudomonas aeruginosa
title Poly-L-Lysine to Fight Antibiotic Resistances of Pseudomonas aeruginosa
title_full Poly-L-Lysine to Fight Antibiotic Resistances of Pseudomonas aeruginosa
title_fullStr Poly-L-Lysine to Fight Antibiotic Resistances of Pseudomonas aeruginosa
title_full_unstemmed Poly-L-Lysine to Fight Antibiotic Resistances of Pseudomonas aeruginosa
title_short Poly-L-Lysine to Fight Antibiotic Resistances of Pseudomonas aeruginosa
title_sort poly-l-lysine to fight antibiotic resistances of pseudomonas aeruginosa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917869/
https://www.ncbi.nlm.nih.gov/pubmed/36769174
http://dx.doi.org/10.3390/ijms24032851
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