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

Salcedo-Sora, Jesus Enrique, Robison, Amy TR, Zaengle-Barone, Jacqueline, Franz, Katherine J and Kell, Douglas B ORCID: 0000-0001-5838-7963 (2021) Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli. MOLECULES, 26 (19). 5826-.

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Official URL: http://dx.doi.org/10.3390/molecules26195826

Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	pyrithione, metal ions, membrane transporters, gram-negative, E. coli, Keio collection, copper, zinc, iron
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology Faculty of Health and Life Sciences > Tech, Infrastructure and Environmental Directorate
Depositing User:	Symplectic Admin
Date Deposited:	17 Jan 2022 10:16
Last Modified:	18 Jan 2023 21:15
DOI:	10.3390/molecules26195826
Open Access URL:	https://doi.org/10.3390/molecules26195826
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3146996