How sex hormones help gonorrhea fight antimicrobials and antibiotics

Oral contraceptive packages warn that the medication will not prevent STIs. In the case of gonorrhea, the sexually transmitted bacteria that causes the disease can use these hormones to help it resist the onslaught of antibiotics.

Like many bacteria, this insect, Neisseria gonorrhoeae, is equipped with pumps to expel deadly chemicals out of its cells. But what is unique, according to a study by Duke and Emory published in Natural communicationsis that hormones in the human urogenital tract actually allow gonorrhea to make and use more of these pumps to combat intrinsic antimicrobials and prescribed antibiotics.

The researchers discovered the trick by looking at a transcription factor, a protein that binds to specific sites on the bacteria’s DNA and slows down the 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 form and function of the transcription factor.

They discovered that unfortunately, this transcription factor, called MtrR, has an affinity for binding to the steroid hormones progesterone, estrogen and testosterone as well as the synthetic hormone ethinylestradiol. When it binds to a hormone, the transcription factor becomes less effective at suppressing the production of bacterial pumps.

Hooks explained that the bacteria appears to be able to sense its hormonal environment and waits for the right moment in a woman’s menstrual cycle to accelerate its colonization.

Estrogen increases significantly in the week before ovulation, and progesterone peaks in the two weeks between ovulation and your period. These fluctuations are thought to suppress the immune system, giving sperm and eggs a window of opportunity to survive in the urogenital tract, but this same window also creates vulnerability to this infection.

“It’s kind of using that sensory system to assess 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 be really good at sensing where it is and when is the best time to colonize.”

The transcription factor MtrR also helps signal the bacteria to protect itself against reactive oxygen species. “This protein acts as a dual system to protect Neisseria gonorrhea,” Brennan said.

Gonorrhea has been around much longer than antibiotics, appearing in texts as old as 2600 BC and making famous appearances in Julius Caesar’s Roman legions and the Crimean War.

Old or not, the Centers for Disease Control considers gonorrhea an urgent public health threat because it is now resistant to all but one antibiotic, ceftriaxone. But strains resistant to this antibiotic have recently been identified in Europe and Asia.

Historically and colloquially known as the “clap,” untreated gonorrhea in women can lead to pelvic inflammatory disease and infertility. It can also be transmitted from mother to child during childbirth.

Although the infection is more obvious in men, it is less dramatic because men don’t experience greater hormonal changes and their urogenital tract is not as complicated or deep as a woman’s, Hooks said. . But men still carry the same hormones that the transcription factor attaches to, she added.

And of course, the bacteria must thrive in both men and women for an STI to be successful. “Neisseria gonorrhoeae is an obligate human pathogen,” Brennan said. “The rest of the time we don’t know where he is.”

When Hooks presented some of his data at a lab meeting, Emily Cannistraci, a graduate student in the nearby Schumacher lab, asked whether the synthetic hormone ethinyl estradiol, found in many women’s oral contraceptives, would have a similar effect. Hooks checked out, and it certainly does.

The takeaway is not only the warning that oral contraception won’t prevent STIs, but in this case, it could even make them worse.