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

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

Journal Article · 07 February 2024 · Nature Communications

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

^[1]; Ayala, Julio C. ^[2]; Holley, Concerta L. ^[3]; Dhulipala, Vijaya ^[3];

^[4]; Perfect, John R. ^[1];

^[1]; Shafer, William M. ^[5];

^[1]

Duke Univ., Durham, NC (United States)
Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States); Emory Univ., Atlanta, GA (United States)
Emory Univ., Atlanta, GA (United States)
Princeton Univ., NJ (United States)
Emory Univ., Atlanta, GA (United States); Veterans Affairs Medical Center, Decatur, GA (United States)

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

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

OSTI ID:: 2290378

Alternate ID(s):: OSTI ID: 2471075

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

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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