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

Hooks, Grace M.; Ayala, Julio C.; Holley, Concerta L.; Dhulipala, Vijaya; Beggs, Grace A.; Perfect, John R.; Schumacher, Maria A.; Shafer, William M.; Brennan, Richard G.

doi:10.1038/s41467-024-45195-1

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

Journal Article · Wed Feb 07 00:00:00 EST 2024 · Nature Communications

DOI:https://doi.org/10.1038/s41467-024-45195-1· OSTI ID:2290378

; Ayala, Julio C.; Holley, Concerta L.; Dhulipala, Vijaya; ; Perfect, John R.; ; Shafer, William M.;

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences & Engineering Division (MSE)

Grant/Contract Number:: AC02-05CH11231; AC03-76SF00098

OSTI ID:: 2290378

Alternate ID(s):: OSTI ID: 2471075

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 15; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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