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

Autor: Hooks GM; Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA., Ayala JC; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.; STD Laboratory Reference and Research Branch, Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA., Holley CL; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA., Dhulipala V; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA., Beggs GA; Department of Molecular Biology, Princeton University, Princeton, NJ, USA., Perfect JR; Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA., Schumacher MA; Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA., Shafer WM; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.; Laboratories of Microbial Pathogenesis, VA Medical Research Service, Veterans Affairs Medical Center, Decatur, GA, USA.; Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA, USA., Brennan RG; Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA. richard.brennan@duke.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 07; Vol. 15 (1), pp. 1153. Date of Electronic Publication: 2024 Feb 07.
DOI: 10.1038/s41467-024-45195-1
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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