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Steroid drugs inhibit bacterial respiratory oxidases and are lethal towards methicillin-resistant Staphylococcus aureus

Henry, Samantha A., Webster, Calum M., Shaw, Lindsey N., Torres, Nathanial J, Jobson, Mary-Elizabeth, Totzke, Brenden C, Jackson, Jessica K, McGreig, Jake E., Wass, Mark N., Robinson, Gary K., and others. (2024) Steroid drugs inhibit bacterial respiratory oxidases and are lethal towards methicillin-resistant Staphylococcus aureus. Journal of Infectious Diseases, . Article Number jiad540. ISSN 0022-1899. E-ISSN 1537-6613. (doi:10.1093/infdis/jiad540) (KAR id:103989)

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Background: Cytochrome bd complexes are respiratory oxidases found exclusively in prokaryotes that are important during infection for numerous bacterial pathogens.

Methods: In silico docking was employed to screen approved drugs for their ability to bind to the quinol site of Escherichia coli cytochrome bd-I. Respiratory inhibition was assessed with oxygen electrodes using membranes isolated from E. coli and Methicillin-resistant Staphylococcus aureus strains expressing single respiratory oxidases (i.e., cytochromes bd, bo or aa3). Growth/viability assays were used to measure bacteriostatic and bactericidal effects.

Results: The steroid drugs ethinylestradiol and quinestrol inhibited E. coli bd-I activity with IC50 values of 47 ± 28.9 µg/mL (158 ± 97.2 µM) and 0.2 ± 0.04 µg/mL (0.5 ± 0.1 µM), respectively. Quinestrol inhibited growth of an E. coli ‘bd-I only’ strain with an IC50 of 0.06 ± 0.02 µg/mL (0.2 ± 0.07 µM). Growth of a S. aureus ‘bd only’ strain was inhibited by quinestrol with an IC50 of 2.2 ± 0.43 µg/mL (6.0 ± 1.2 µM). Quinestrol exhibited potent bactericidal effects against S. aureus but not E. coli.

Conclusions: Quinestrol inhibits cytochrome bd in E. coli and S. aureus membranes and inhibits the growth of both species yet is only bactericidal towards S. aureus.

Item Type: Article
DOI/Identification number: 10.1093/infdis/jiad540
Uncontrolled keywords: cytochrome bd, antimicrobials, drug repurposing, quinestrol, MRSA
Subjects: Q Science > QR Microbiology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: University of Kent (
National Institutes of Health (
Depositing User: Mark Shepherd
Date Deposited: 21 Nov 2023 09:19 UTC
Last Modified: 28 Feb 2024 11:31 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

Webster, Calum M..

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McGreig, Jake E..

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Wass, Mark N..

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Robinson, Gary K..

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Shepherd, Mark.

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