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Steroid Drugs Inhibit Bacterial Respiratory Oxidases and Are Lethal Toward Methicillin-Resistant Staphylococcus aureus.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2024 Jul 25; Vol. 230 (1), pp. e149-e158. - Publication Year :
- 2024
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Abstract
- Background: Cytochrome bd complexes are respiratory oxidases found exclusively in prokaryotes that are important during infection for numerous bacterial pathogens.<br />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 (ie, cytochromes bd, bo', or aa3). Growth/viability assays were used to measure bacteriostatic and bactericidal effects.<br />Results: The steroid drugs ethinylestradiol and quinestrol inhibited E. coli bd-I activity with median inhibitory concentration (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 an 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.<br />Conclusions: Quinestrol inhibits cytochrome bd in E. coli and S. aureus membranes and inhibits the growth of both species, yet is only bactericidal toward S. aureus.<br />Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Subjects :
- Molecular Docking Simulation
Oxidoreductases antagonists & inhibitors
Oxidoreductases metabolism
Escherichia coli Proteins antagonists & inhibitors
Escherichia coli Proteins metabolism
Microbial Sensitivity Tests
Steroids pharmacology
Steroids chemistry
Electron Transport Chain Complex Proteins antagonists & inhibitors
Electron Transport Chain Complex Proteins metabolism
Cytochrome b Group
Cytochromes antagonists & inhibitors
Cytochromes metabolism
Methicillin-Resistant Staphylococcus aureus drug effects
Escherichia coli drug effects
Escherichia coli enzymology
Anti-Bacterial Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 230
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 39052707
- Full Text :
- https://doi.org/10.1093/infdis/jiad540