Phenotypic Adaptation of <i>Pseudomonas aeruginosa</i> 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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MDPI AG
2020-11-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/8/11/1820 |
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| author | Quentin Perraud Paola Cantero Mathilde Munier Françoise Hoegy Nicolas Zill Véronique Gasser Gaëtan L. A. Mislin Laurence Ehret-Sabatier Isabelle J. Schalk |
| author_facet | Quentin Perraud Paola Cantero Mathilde Munier Françoise Hoegy Nicolas Zill Véronique Gasser Gaëtan L. A. Mislin Laurence Ehret-Sabatier Isabelle J. Schalk |
| author_sort | Quentin Perraud |
| collection | DOAJ |
| 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. <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> 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. |
| first_indexed | 2024-03-10T14:45:19Z |
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| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T14:45:19Z |
| publishDate | 2020-11-01 |
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| series | Microorganisms |
| spelling | doaj.art-e8a9311ad2074f619f3a9dec1b99484a2023-11-20T21:27:58ZengMDPI AGMicroorganisms2076-26072020-11-01811182010.3390/microorganisms8111820Phenotypic Adaptation of <i>Pseudomonas aeruginosa</i> in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell InfectionQuentin Perraud0Paola Cantero1Mathilde Munier2Françoise Hoegy3Nicolas Zill4Véronique Gasser5Gaëtan L. A. Mislin6Laurence Ehret-Sabatier7Isabelle J. Schalk8CNRS, UMR7242, ESBS, Bd Sébastien Brant, Illkirch, F-67413 Strasbourg, FranceLaboratoire de Spectrométrie de Masse BioOrganique, Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, FranceCNRS, UMR7242, ESBS, Bd Sébastien Brant, Illkirch, F-67413 Strasbourg, FranceCNRS, UMR7242, ESBS, Bd Sébastien Brant, Illkirch, F-67413 Strasbourg, FranceCNRS, UMR7242, ESBS, Bd Sébastien Brant, Illkirch, F-67413 Strasbourg, FranceCNRS, UMR7242, ESBS, Bd Sébastien Brant, Illkirch, F-67413 Strasbourg, FranceCNRS, UMR7242, ESBS, Bd Sébastien Brant, Illkirch, F-67413 Strasbourg, FranceLaboratoire de Spectrométrie de Masse BioOrganique, Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000 Strasbourg, FranceCNRS, UMR7242, ESBS, Bd Sébastien Brant, Illkirch, F-67413 Strasbourg, FranceIron 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. <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> 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.https://www.mdpi.com/2076-2607/8/11/1820siderophoresiderophore–antibiotic<i>Pseudomonas aeruginosa</i>TonB dependent transportersiron uptakeproteomic |
| spellingShingle | Quentin Perraud Paola Cantero Mathilde Munier Françoise Hoegy Nicolas Zill Véronique Gasser Gaëtan L. A. Mislin Laurence Ehret-Sabatier Isabelle J. Schalk Phenotypic Adaptation of <i>Pseudomonas aeruginosa</i> in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection Microorganisms siderophore siderophore–antibiotic <i>Pseudomonas aeruginosa</i> TonB dependent transporters iron uptake proteomic |
| title | Phenotypic Adaptation of <i>Pseudomonas aeruginosa</i> in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection |
| title_full | Phenotypic Adaptation of <i>Pseudomonas aeruginosa</i> in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection |
| title_fullStr | Phenotypic Adaptation of <i>Pseudomonas aeruginosa</i> in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection |
| title_full_unstemmed | Phenotypic Adaptation of <i>Pseudomonas aeruginosa</i> in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection |
| title_short | Phenotypic Adaptation of <i>Pseudomonas aeruginosa</i> in the Presence of Siderophore-Antibiotic Conjugates during Epithelial Cell Infection |
| title_sort | phenotypic adaptation of i pseudomonas aeruginosa i in the presence of siderophore antibiotic conjugates during epithelial cell infection |
| topic | siderophore siderophore–antibiotic <i>Pseudomonas aeruginosa</i> TonB dependent transporters iron uptake proteomic |
| url | https://www.mdpi.com/2076-2607/8/11/1820 |
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