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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Salcedo-Sora, JE; Robison, ATR; Zaengle-Barone, J; Franz, KJ; Kell, DB

Published Date

  • September 26, 2021

Published In

Volume / Issue

  • 26 / 19

PubMed ID

  • 34641370

Pubmed Central ID

  • PMC8510280

Electronic International Standard Serial Number (EISSN)

  • 1420-3049

International Standard Serial Number (ISSN)

  • 1420-3049

Digital Object Identifier (DOI)

  • 10.3390/molecules26195826

Language

  • eng