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.

Transcriptional regulator MtrR inhibits the expression of the multidrug efflux pump operon mtrCDE in Neisseria gonorrhoeae. Here, Hooks et al. show that hormonal steroids bind to MtrR and decrease its affinity for cognate promoters, thus leading to increased mtrCDE expression and enhanced antimicrobial resistance.

Details

Title
Hormonal steroids induce multidrug resistance and stress response genes in Neisseria gonorrhoeae by binding to MtrR
Author
Hooks, Grace M. 1   VIAFID ORCID Logo  ; Ayala, Julio C. 2 ; Holley, Concerta L. 3 ; Dhulipala, Vijaya 3 ; Beggs, Grace A. 4   VIAFID ORCID Logo  ; Perfect, John R. 5 ; Schumacher, Maria A. 1   VIAFID ORCID Logo  ; Shafer, William M. 6 ; Brennan, Richard G. 1   VIAFID ORCID Logo 

1  Duke University School of Medicine, Department of Biochemistry, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961) 
2  Emory University School of Medicine, Department of Microbiology and Immunology, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502); Centers for Disease Control and Prevention, STD Laboratory Reference and Research Branch, Division of STD Prevention, Atlanta, USA (GRID:grid.416738.f) (ISNI:0000 0001 2163 0069) 
3  Emory University School of Medicine, Department of Microbiology and Immunology, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502) 
4  Princeton University, Department of Molecular Biology, Princeton, USA (GRID:grid.16750.35) (ISNI:0000 0001 2097 5006) 
5  Duke University Medical Center, Division of Infectious Diseases, Department of Medicine, Durham, USA (GRID:grid.189509.c) (ISNI:0000 0001 0024 1216) 
6  Emory University School of Medicine, Department of Microbiology and Immunology, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502); Veterans Affairs Medical Center, Laboratories of Microbial Pathogenesis, VA Medical Research Service, Decatur, USA (GRID:grid.414026.5) (ISNI:0000 0004 0419 4084); Emory University School of Medicine, Emory Antibiotic Resistance Center, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502) 
Pages
1153
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-024-45195-1
ProQuest document ID
2923166849
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.