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Evaluation of phages and liposomes as combination therapy to counteract Pseudomonas aeruginosa infection in wild-type and CFTR-null models

Multi drug resistant (MDR) bacteria are insensitive to the most common antibiotics currently in use. The spread of antibiotic-resistant bacteria, if not contained, will represent the main cause of death for humanity in 2050. The situation is even more worrying when considering patients with chronic...

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Autores principales: Cafora, Marco, Poerio, Noemi, Forti, Francesca, Loberto, Nicoletta, Pin, Davide, Bassi, Rosaria, Aureli, Massimo, Briani, Federica, Pistocchi, Anna, Fraziano, Maurizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520727/
https://www.ncbi.nlm.nih.gov/pubmed/36188006
http://dx.doi.org/10.3389/fmicb.2022.979610
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author Cafora, Marco
Poerio, Noemi
Forti, Francesca
Loberto, Nicoletta
Pin, Davide
Bassi, Rosaria
Aureli, Massimo
Briani, Federica
Pistocchi, Anna
Fraziano, Maurizio
author_facet Cafora, Marco
Poerio, Noemi
Forti, Francesca
Loberto, Nicoletta
Pin, Davide
Bassi, Rosaria
Aureli, Massimo
Briani, Federica
Pistocchi, Anna
Fraziano, Maurizio
author_sort Cafora, Marco
collection PubMed
description Multi drug resistant (MDR) bacteria are insensitive to the most common antibiotics currently in use. The spread of antibiotic-resistant bacteria, if not contained, will represent the main cause of death for humanity in 2050. The situation is even more worrying when considering patients with chronic bacterial infections, such as those with Cystic Fibrosis (CF). The development of alternative approaches is essential and novel therapies that combine exogenous and host-mediated antimicrobial action are promising. In this work, we demonstrate that asymmetric phosphatidylserine/phosphatidic acid (PS/PA) liposomes administrated both in prophylactic and therapeutic treatments, induced a reduction in the bacterial burden both in wild-type and cftr-loss-of-function (cftr-LOF) zebrafish embryos infected with Pseudomonas aeruginosa (Pa) PAO1 strain (PAO1). These effects are elicited through the enhancement of phagocytic activity of macrophages. Moreover, the combined use of liposomes and a phage-cocktail (CKΦ), already validated as a PAO1 “eater”, improves the antimicrobial effects of single treatments, and it is effective also against CKΦ-resistant bacteria. We also address the translational potential of the research, by evaluating the safety of CKΦ and PS/PA liposomes administrations in in vitro model of human bronchial epithelial cells, carrying the homozygous F508del-CFTR mutation, and in THP-1 cells differentiated into a macrophage-like phenotype with pharmacologically inhibited CFTR. Our results open the way to the development of novel pharmacological formulations composed of both phages and liposomes to counteract more efficiently the infections caused by Pa or other bacteria, especially in patients with chronic infections such those with CF.
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spelling pubmed-95207272022-09-30 Evaluation of phages and liposomes as combination therapy to counteract Pseudomonas aeruginosa infection in wild-type and CFTR-null models Cafora, Marco Poerio, Noemi Forti, Francesca Loberto, Nicoletta Pin, Davide Bassi, Rosaria Aureli, Massimo Briani, Federica Pistocchi, Anna Fraziano, Maurizio Front Microbiol Microbiology Multi drug resistant (MDR) bacteria are insensitive to the most common antibiotics currently in use. The spread of antibiotic-resistant bacteria, if not contained, will represent the main cause of death for humanity in 2050. The situation is even more worrying when considering patients with chronic bacterial infections, such as those with Cystic Fibrosis (CF). The development of alternative approaches is essential and novel therapies that combine exogenous and host-mediated antimicrobial action are promising. In this work, we demonstrate that asymmetric phosphatidylserine/phosphatidic acid (PS/PA) liposomes administrated both in prophylactic and therapeutic treatments, induced a reduction in the bacterial burden both in wild-type and cftr-loss-of-function (cftr-LOF) zebrafish embryos infected with Pseudomonas aeruginosa (Pa) PAO1 strain (PAO1). These effects are elicited through the enhancement of phagocytic activity of macrophages. Moreover, the combined use of liposomes and a phage-cocktail (CKΦ), already validated as a PAO1 “eater”, improves the antimicrobial effects of single treatments, and it is effective also against CKΦ-resistant bacteria. We also address the translational potential of the research, by evaluating the safety of CKΦ and PS/PA liposomes administrations in in vitro model of human bronchial epithelial cells, carrying the homozygous F508del-CFTR mutation, and in THP-1 cells differentiated into a macrophage-like phenotype with pharmacologically inhibited CFTR. Our results open the way to the development of novel pharmacological formulations composed of both phages and liposomes to counteract more efficiently the infections caused by Pa or other bacteria, especially in patients with chronic infections such those with CF. Frontiers Media S.A. 2022-09-15 /pmc/articles/PMC9520727/ /pubmed/36188006 http://dx.doi.org/10.3389/fmicb.2022.979610 Text en Copyright © 2022 Cafora, Poerio, Forti, Loberto, Pin, Bassi, Aureli, Briani, Pistocchi and Fraziano. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Cafora, Marco
Poerio, Noemi
Forti, Francesca
Loberto, Nicoletta
Pin, Davide
Bassi, Rosaria
Aureli, Massimo
Briani, Federica
Pistocchi, Anna
Fraziano, Maurizio
Evaluation of phages and liposomes as combination therapy to counteract Pseudomonas aeruginosa infection in wild-type and CFTR-null models
title Evaluation of phages and liposomes as combination therapy to counteract Pseudomonas aeruginosa infection in wild-type and CFTR-null models
title_full Evaluation of phages and liposomes as combination therapy to counteract Pseudomonas aeruginosa infection in wild-type and CFTR-null models
title_fullStr Evaluation of phages and liposomes as combination therapy to counteract Pseudomonas aeruginosa infection in wild-type and CFTR-null models
title_full_unstemmed Evaluation of phages and liposomes as combination therapy to counteract Pseudomonas aeruginosa infection in wild-type and CFTR-null models
title_short Evaluation of phages and liposomes as combination therapy to counteract Pseudomonas aeruginosa infection in wild-type and CFTR-null models
title_sort evaluation of phages and liposomes as combination therapy to counteract pseudomonas aeruginosa infection in wild-type and cftr-null models
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520727/
https://www.ncbi.nlm.nih.gov/pubmed/36188006
http://dx.doi.org/10.3389/fmicb.2022.979610
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