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Article

Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli

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Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Crown St., Liverpool L69 7ZB, UK
2
Department of Chemistry, Duke University, 124 Science Drive, Durham, NC 27708, USA
3
Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet, 2800 Kgs Lyngby, Denmark
*
Authors to whom correspondence should be addressed.
Academic Editor: Mary K. Phillips-Jones
Molecules 2021, 26(19), 5826; https://doi.org/10.3390/molecules26195826
Received: 29 July 2021 / Revised: 16 September 2021 / Accepted: 20 September 2021 / Published: 26 September 2021
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 E. coli 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. View Full-Text
Keywords: pyrithione; metal ions; membrane transporters; gram-negative; E. coli; Keio collection; copper; zinc; iron pyrithione; metal ions; membrane transporters; gram-negative; E. coli; Keio collection; copper; zinc; iron
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MDPI and ACS Style

Salcedo-Sora, J.E.; Robison, A.T.R.; Zaengle-Barone, J.; Franz, K.J.; Kell, D.B. Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli. Molecules 2021, 26, 5826. https://doi.org/10.3390/molecules26195826

AMA Style

Salcedo-Sora JE, Robison ATR, Zaengle-Barone J, Franz KJ, Kell DB. Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli. Molecules. 2021; 26(19):5826. https://doi.org/10.3390/molecules26195826

Chicago/Turabian Style

Salcedo-Sora, Jesus Enrique, Amy T. R. Robison, Jacqueline Zaengle-Barone, Katherine J. Franz, and Douglas B. Kell. 2021. "Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli" Molecules 26, no. 19: 5826. https://doi.org/10.3390/molecules26195826

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