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Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection

Iron acquisition pathways have often been considered to be gateways for the uptake of antibiotics into bacteria. Bacteria excrete chelators, called siderophores, to access iron. Antibiotic molecules can be covalently attached to siderophores for their transport into pathogens during the iron-uptake...

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Autores principales: Perraud, Quentin, Cantero, Paola, Munier, Mathilde, Hoegy, Françoise, Zill, Nicolas, Gasser, Véronique, Mislin, Gaëtan L. A., Ehret-Sabatier, Laurence, Schalk, Isabelle J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699141/
https://www.ncbi.nlm.nih.gov/pubmed/33218210
http://dx.doi.org/10.3390/microorganisms8111820
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author Perraud, Quentin
Cantero, Paola
Munier, Mathilde
Hoegy, Françoise
Zill, Nicolas
Gasser, Véronique
Mislin, Gaëtan L. A.
Ehret-Sabatier, Laurence
Schalk, Isabelle J.
author_facet Perraud, Quentin
Cantero, Paola
Munier, Mathilde
Hoegy, Françoise
Zill, Nicolas
Gasser, Véronique
Mislin, Gaëtan L. A.
Ehret-Sabatier, Laurence
Schalk, Isabelle J.
author_sort Perraud, Quentin
collection PubMed
description Iron acquisition pathways have often been considered to be gateways for the uptake of antibiotics into bacteria. Bacteria excrete chelators, called siderophores, to access iron. Antibiotic molecules can be covalently attached to siderophores for their transport into pathogens during the iron-uptake process. P. aeruginosa produces two siderophores and is also able to use many siderophores produced by other bacteria. We investigated the phenotypic plasticity of iron-uptake pathway expression in an epithelial cell infection assay in the presence of two different siderophore–antibiotic conjugates, one with a hydroxamate siderophore and the second with a tris-catechol. Proteomic and RT-qPCR approaches showed that P. aeruginosa was able to sense the presence of both compounds in its environment and adapt the expression of its iron uptake pathways to access iron via them. Moreover, the catechol-type siderophore–antibiotic was clearly more efficient in inducing the expression of its corresponding transporter than the hydroxamate compound when both were simultaneously present. In parallel, the expression of the proteins of the two iron uptake pathways using siderophores produced by P. aeruginosa was significantly repressed in the presence of both conjugates. Altogether, the data indicate that catechol-type siderophores are more promising vectors for antibiotic vectorization using a Trojan-horse strategy.
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spelling pubmed-76991412020-11-29 Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection Perraud, Quentin Cantero, Paola Munier, Mathilde Hoegy, Françoise Zill, Nicolas Gasser, Véronique Mislin, Gaëtan L. A. Ehret-Sabatier, Laurence Schalk, Isabelle J. Microorganisms Article Iron acquisition pathways have often been considered to be gateways for the uptake of antibiotics into bacteria. Bacteria excrete chelators, called siderophores, to access iron. Antibiotic molecules can be covalently attached to siderophores for their transport into pathogens during the iron-uptake process. P. aeruginosa produces two siderophores and is also able to use many siderophores produced by other bacteria. We investigated the phenotypic plasticity of iron-uptake pathway expression in an epithelial cell infection assay in the presence of two different siderophore–antibiotic conjugates, one with a hydroxamate siderophore and the second with a tris-catechol. Proteomic and RT-qPCR approaches showed that P. aeruginosa was able to sense the presence of both compounds in its environment and adapt the expression of its iron uptake pathways to access iron via them. Moreover, the catechol-type siderophore–antibiotic was clearly more efficient in inducing the expression of its corresponding transporter than the hydroxamate compound when both were simultaneously present. In parallel, the expression of the proteins of the two iron uptake pathways using siderophores produced by P. aeruginosa was significantly repressed in the presence of both conjugates. Altogether, the data indicate that catechol-type siderophores are more promising vectors for antibiotic vectorization using a Trojan-horse strategy. MDPI 2020-11-18 /pmc/articles/PMC7699141/ /pubmed/33218210 http://dx.doi.org/10.3390/microorganisms8111820 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Perraud, Quentin
Cantero, Paola
Munier, Mathilde
Hoegy, Françoise
Zill, Nicolas
Gasser, Véronique
Mislin, Gaëtan L. A.
Ehret-Sabatier, Laurence
Schalk, Isabelle J.
Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection
title Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection
title_full Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection
title_fullStr Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection
title_full_unstemmed Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection
title_short Phenotypic Adaptation of Pseudomonas aeruginosa in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection
title_sort phenotypic adaptation of pseudomonas aeruginosa in the presence of siderophore-antibiotic conjugates during epithelial cell infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699141/
https://www.ncbi.nlm.nih.gov/pubmed/33218210
http://dx.doi.org/10.3390/microorganisms8111820
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