Rates of sexually transmitted infections (STIs) were getting lower in the United States for many years, but that trend has recently reversed, and STI rates are now skyrocketing. Gonorrhea is one of many STIs that has gotten significantly more common, and in 2022 alone, almost 650,000 cases were reported in the US. Worldwide, an estimated 85 million individuals are affected by the sexually transmitted bacterial infection every year. Oral contraception can prevent pregnancy, but it does nothing to protect against STIs. Now, research has even suggested that oral contraception can actually help the bacteria that causes gonorrhea, Neisseria gonorrhoeae, resist the effects of antibiotics. The findings have been reported in Nature Communications.
N. gonorrhoeae is bacterial pathogen that has molecular pumps that can remove antibiotics from inside itself. But hormones in the human urogenital tract help the microbe make more of these pumps so that it is better at resisting antimicrobial molecules produced by the body, or prescription antibiotics.
In this work, the researchers determined that N. gonorrhoeae carries a transcription factor, a molecule that helps control gene expression, called MtrR. This transcription factor likes to bind to hormones, including estrogen, progesterone, and testosterone, as well as the synthetic hormone ethinylestradiol, found in many birth control tablets. MtrR releases the brakes on the production of bacterial pumps, leading to the production of more of the pumps.
The investigators aimed to characterize this transcription factor, which seems to sense hormones in its environment. MtrR can take advantage of the female hormonal cycle and wait for the best time to promote growth, explained first study author and graduate student Grace Hooks. In the week before ovulation, estrogen levels rise; while progesterone levels are highest between menstruation and ovulation.
"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."
MtrR can also help shield the pathogen from reactive oxygen species. "What this one protein does is a dual system to protect Neisseria gonorrhea," said senior study author Richard Brennan, PhD, the Chair of Biochemistry at Duke University.
Gonorrhea has been infecting humans for thousands of years, and it is now resistant to every antibiotic other than a drug called ceftriaxone, which is now not effective against every strain. That means that the pathogen has evolved to gain resistance against aminoglycosides, beta-lactams, fluoroquinolones, macrolides, sulfonamides, and tetracyclines. Ceftriaxone-resisjtant gonorrhea has also been identified in Europe and Asia, which means some strains are resistant to every available drug, and untreatable strains appear to be emerging.
Infections don't always cause symptoms in women, and if untreated, it can cause pelvic inflammatory disease and infertility. Newborns can also contract the STI during childbirth, and it may cause blindness in those individuals. Men don't have as many hormonal shifts as women, which could explain why the infection is not as severe in men. However, they can still get the disease and pass it on.
"Neisseria gonorrhoeae is an obligate human pathogen," Brennan added. "We don't know where it is the rest of the time."
Sources: Duke University, Nature Communications
