Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in <i>Escherichia coli</i>
Pyrithione (2-mercaptopyridine-N-oxide) is a metal binding modified pyridine, the antibacterial activity of which was described over 60 years ago. The formulation of zinc-pyrithione is commonly used in the topical treatment of certain dermatological conditions. However, the characterisation of the c...
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MDPI AG
2021-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/19/5826 |
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| author | Jesus Enrique Salcedo-Sora Amy T. R. Robison Jacqueline Zaengle-Barone Katherine J. Franz Douglas B. Kell |
| author_facet | Jesus Enrique Salcedo-Sora Amy T. R. Robison Jacqueline Zaengle-Barone Katherine J. Franz Douglas B. Kell |
| author_sort | Jesus Enrique Salcedo-Sora |
| collection | DOAJ |
| description | Pyrithione (2-mercaptopyridine-N-oxide) is a metal binding modified pyridine, the antibacterial activity of which was described over 60 years ago. The formulation of zinc-pyrithione is commonly used in the topical treatment of certain dermatological conditions. However, the characterisation of the cellular uptake of pyrithione has not been elucidated, although an unsubstantiated assumption has persisted that pyrithione and/or its metal complexes undergo a passive diffusion through cell membranes. Here, we have profiled specific membrane transporters from an unbiased interrogation of 532 <i>E. coli</i> strains of knockouts of genes encoding membrane proteins from the Keio collection. Two membrane transporters, FepC and MetQ, seemed involved in the uptake of pyrithione and its cognate metal complexes with copper, iron, and zinc. Additionally, the phenotypes displayed by CopA and ZntA knockouts suggested that these two metal effluxers drive the extrusion from the bacterial cell of potentially toxic levels of copper, and perhaps zinc, which hyperaccumulate as a function of pyrithione. The involvement of these distinct membrane transporters contributes to the understanding of the mechanisms of action of pyrithione specifically and highlights, more generally, the important role that membrane transporters play in facilitating the uptake of drugs, including metal–drug compounds. |
| first_indexed | 2024-03-10T06:54:48Z |
| format | Article |
| id | doaj.art-34fea5a9bb0c42c4be9b3b54b70c0dca |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T06:54:48Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-34fea5a9bb0c42c4be9b3b54b70c0dca2023-11-22T16:33:14ZengMDPI AGMolecules1420-30492021-09-012619582610.3390/molecules26195826Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in <i>Escherichia coli</i>Jesus Enrique Salcedo-Sora0Amy T. R. Robison1Jacqueline Zaengle-Barone2Katherine J. Franz3Douglas B. Kell4Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Crown St., Liverpool L69 7ZB, UKDepartment of Chemistry, Duke University, 124 Science Drive, Durham, NC 27708, USADepartment of Chemistry, Duke University, 124 Science Drive, Durham, NC 27708, USADepartment of Chemistry, Duke University, 124 Science Drive, Durham, NC 27708, USADepartment of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Crown St., Liverpool L69 7ZB, UKPyrithione (2-mercaptopyridine-N-oxide) is a metal binding modified pyridine, the antibacterial activity of which was described over 60 years ago. The formulation of zinc-pyrithione is commonly used in the topical treatment of certain dermatological conditions. However, the characterisation of the cellular uptake of pyrithione has not been elucidated, although an unsubstantiated assumption has persisted that pyrithione and/or its metal complexes undergo a passive diffusion through cell membranes. Here, we have profiled specific membrane transporters from an unbiased interrogation of 532 <i>E. coli</i> strains of knockouts of genes encoding membrane proteins from the Keio collection. Two membrane transporters, FepC and MetQ, seemed involved in the uptake of pyrithione and its cognate metal complexes with copper, iron, and zinc. Additionally, the phenotypes displayed by CopA and ZntA knockouts suggested that these two metal effluxers drive the extrusion from the bacterial cell of potentially toxic levels of copper, and perhaps zinc, which hyperaccumulate as a function of pyrithione. The involvement of these distinct membrane transporters contributes to the understanding of the mechanisms of action of pyrithione specifically and highlights, more generally, the important role that membrane transporters play in facilitating the uptake of drugs, including metal–drug compounds.https://www.mdpi.com/1420-3049/26/19/5826pyrithionemetal ionsmembrane transportersgram-negative<i>E. coli</i>Keio collection |
| spellingShingle | Jesus Enrique Salcedo-Sora Amy T. R. Robison Jacqueline Zaengle-Barone Katherine J. Franz Douglas B. Kell Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in <i>Escherichia coli</i> Molecules pyrithione metal ions membrane transporters gram-negative <i>E. coli</i> Keio collection |
| title | Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in <i>Escherichia coli</i> |
| title_full | Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in <i>Escherichia coli</i> |
| title_fullStr | Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in <i>Escherichia coli</i> |
| title_full_unstemmed | Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in <i>Escherichia coli</i> |
| title_short | Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in <i>Escherichia coli</i> |
| title_sort | membrane transporters involved in the antimicrobial activities of pyrithione in i escherichia coli i |
| topic | pyrithione metal ions membrane transporters gram-negative <i>E. coli</i> Keio collection |
| url | https://www.mdpi.com/1420-3049/26/19/5826 |
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