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

Publication ,  Journal Article
Salcedo-Sora, JE; Robison, ATR; Zaengle-Barone, J; Franz, KJ; Kell, DB
Published in: Molecules (Basel, Switzerland)
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.

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Published In

Molecules (Basel, Switzerland)

DOI

EISSN

1420-3049

ISSN

1420-3049

Publication Date

September 2021

Volume

26

Issue

19

Start / End Page

5826

Related Subject Headings

  • Thiones
  • Pyridines
  • Organic Chemistry
  • Metals
  • Membrane Transport Proteins
  • Escherichia coli Proteins
  • Escherichia coli
  • Copper-transporting ATPases
  • Copper-Transporting ATPases
  • Anti-Bacterial Agents
 

Citation

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Salcedo-Sora, J. E., Robison, A. T. R., Zaengle-Barone, J., Franz, K. J., & Kell, D. B. (2021). Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli. Molecules (Basel, Switzerland), 26(19), 5826. https://doi.org/10.3390/molecules26195826
Salcedo-Sora, Jesus Enrique, Amy T. R. Robison, Jacqueline Zaengle-Barone, Katherine J. Franz, and Douglas B. Kell. “Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli.Molecules (Basel, Switzerland) 26, no. 19 (September 2021): 5826. https://doi.org/10.3390/molecules26195826.
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 (Basel, Switzerland). 2021 Sep;26(19):5826.
Salcedo-Sora, Jesus Enrique, et al. “Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli.Molecules (Basel, Switzerland), vol. 26, no. 19, Sept. 2021, p. 5826. Epmc, doi:10.3390/molecules26195826.
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 (Basel, Switzerland). 2021 Sep;26(19):5826.

Published In

Molecules (Basel, Switzerland)

DOI

EISSN

1420-3049

ISSN

1420-3049

Publication Date

September 2021

Volume

26

Issue

19

Start / End Page

5826

Related Subject Headings

  • Thiones
  • Pyridines
  • Organic Chemistry
  • Metals
  • Membrane Transport Proteins
  • Escherichia coli Proteins
  • Escherichia coli
  • Copper-transporting ATPases
  • Copper-Transporting ATPases
  • Anti-Bacterial Agents