Sex hormones enhance gonorrhea's defense against antibiotics

The standard warning on oral contraceptives about not protecting against STIs takes on new significance with gonorrhea; the bacterium causing this disease can utilize the hormones from birth control to boost its antibiotic resistance.

Like many bacteria, Neisseria gonorrhoeae, is equipped with pumps to push the killing chemicals out of its cells. But what’s unique, according to a Duke and Emory study online this week in Nature Communications, is that the hormones of the human urogenital tract actually allow gonorrhea to make and use more of these pumps to fight intrinsic antimicrobials and prescribed antibiotics.

The researchers uncovered the information while examining a transcription factor – a protein that binds to specific sites on the bacterium’s DNA and slows production of the efflux pumps that protect it.

Led by Duke graduate student Grace Hooks and her mentor, Biochemistry chair Richard Brennan, Ph.D., the study used a variety of approaches to characterize the shape and function of the transcription factor.

The researchers discovered that a transcription factor known as MtrR exhibits a strong binding affinity for hormonal steroids such as progesterone, estrogen, testosterone, and the synthetic hormone ethinyl estradiol. Upon binding with a hormone, this transcription factor's ability to suppress the bacterial pumps' production diminishes, making it less effective.

“It's kind of utilizing this sensory system to gauge where it is in this cycle and when it can best colonize,” Hooks said. “It can only survive in the human host, it can't survive outside. So, it has to really be good at sensing where it is and when’s the best time for colonizing.”

The transcription factor MtrR also helps signal the bacterium to protect itself against reactive oxygen species. “What this one protein does is a dual system to protect Neisseria gonorrhea,” Brennan said.

For the bacterium to be a successful sexually transmitted infection (STI), it must effectively thrive in both men and women. “Neisseria gonorrhoeae is an obligate human pathogen. We don’t know where it is the rest of the time.” concluded Brennan.

Reference: “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, Richard G. Brennan. Nature Communications, Online Feb. 7, 2024. DOI: 10.1038/s41467-024-45195-1