Have you ever read the package insert warning that oral contraception cannot prevent STIs? Well, in the case of gonorrhea, the sexually transmitted bacterium that causes the disease can actually use these hormones to resist antibiotic attacks.
Like many bacteria, this bug, Neisseria gonorrhea, is equipped with pumps to transport deadly chemicals out of its cells. However, what is unique, as a study from Duke and Emory published this week in Naturkommunication online shows, is that the hormones from the human urogenital tract actually allow gonorrhea to produce and use more of these pumps to fight intrinsic antimicrobials and prescribed antibiotics.
The researchers discovered this mechanism when they were studying a transcription factor – a protein that binds to specific locations on the bacterium’s DNA and slows down the production of bacterial pumps that protect it.
Under the leadership of Duke doctoral student Grace Hooks and her mentor, Biochemistry Chair Richard Brennan, Ph.D., the study used various approaches to characterize the form and function of the transcription factor.
They found that this transcription factor called MtrR unfortunately has an affinity for binding to the hormonal steroids progesterone, estrogen, and testosterone, as well as the synthetic hormone ethinylestradiol. When it binds to a hormone, the transcription factor becomes less effective in suppressing the production of bacterial pumps.
Hooks said the bacterium appears to be able to sense its hormonal environment and wait for the right time in the woman’s menstrual cycle to advance its colonization.
Estrogen rises dramatically in the week before ovulation and progesterone peaks in the two weeks between ovulation and menstruation. These fluctuations are believed to suppress the immune system and give sperm and eggs the opportunity to survive in the urogenital tract. However, the same window of time also creates vulnerability to this infection.
„It’s about utilizing this sensory system to assess where it is in this cycle and when it can best colonize. It can only survive in the human host; it cannot survive outside. So, it really needs to be able to detect very well where it is and when the best time for colonization is.“
Grace Hooks, Duke doctoral student
The transcription factor MtrR also helps the bacterium protect itself from reactive oxygen species. „What this one protein does is it’s a dual system for protection for Neisseria gonorrhea,“ said Brennan.
Gonorrhea has been around in humans much longer than antibiotics have. It already appears in texts from 2600 BC and has had famous appearances in Julius Caesar’s Roman legions and the Crimean War.
Old or not, the Centers for Disease Control view gonorrhea as an urgent public health threat, as it is now resistant to every antibiotic except one, ceftriaxone. However, 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 the mother to the child during childbirth.
While the infection in men is more apparent, it is less dramatic, as men do not experience major hormonal changes and their urogenital tract is not as complicated or deep as that of a woman, Hooks said. But men still carry the same hormones that the transcription factor binds to, she added.
And of course, for a sexually transmitted infection to be successful, the bacteria must thrive in both men and women. „Neisseria gonorrhea is an obligate human pathogen,“ Brennan said. „The rest of the time, we don’t know where it is.“
As Hooks presented some of her data in a laboratory discussion, her colleague Emily Cannistraci from the neighboring Schumacher Lab asked if the synthetic hormone ethinylestradiol, which is present in many oral contraceptives for women, would have a similar effect. Hooks checked, and it certainly did.
The realization goes beyond the warning on the packaging that oral contraception cannot prevent STIs, as in this case, it could even worsen them.
This research was supported by the National Institutes of Health (R35GM130290, R05 AI048593, R01 AI021150), the U.S. Department of Veterans Affairs, and the U.S. Department of Energy.
Haken, GM, et al. (2024). Hormonal steroids induce multi-drug resistance and stress response genes in Neisseria gonorrhea by binding to MtrR. Naturkommunication. doi.org/10.1038/s41467-024-45195-1