Hormonal steroids induce multidrug resistance and stress response genes in Neisseria gonorrhoeae by binding to MtrR

Grace M. Hooks, Julio C. Ayala, Concerta L. Holley, Vijaya Dhulipala, Grace A. Beggs, John R. Perfect, Maria A. Schumacher, William M. Shafer and Richard G. Brennan ()
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Grace M. Hooks: Duke University School of Medicine
Julio C. Ayala: Emory University School of Medicine
Concerta L. Holley: Emory University School of Medicine
Vijaya Dhulipala: Emory University School of Medicine
Grace A. Beggs: Princeton University
John R. Perfect: Duke University Medical Center
Maria A. Schumacher: Duke University School of Medicine
William M. Shafer: Emory University School of Medicine
Richard G. Brennan: Duke University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Transcriptional regulator MtrR inhibits the expression of the multidrug efflux pump operon mtrCDE in the pathogenic bacterium Neisseria gonorrhoeae. Here, we show that MtrR binds the hormonal steroids progesterone, β-estradiol, and testosterone, which are present at urogenital infection sites, as well as ethinyl estrogen, a component of some hormonal contraceptives. Steroid binding leads to the decreased affinity of MtrR for cognate DNA, increased mtrCDE expression, and enhanced antimicrobial resistance. Furthermore, we solve crystal structures of MtrR bound to each steroid, thus revealing their binding mechanisms and the conformational changes that induce MtrR.

Date: 2024
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DOI: 10.1038/s41467-024-45195-1

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