Rates of sexually transmitted infections have been rising since 2000. There are few effective treatment options for syphilis, which was nearly eradicated in the United States at the time and now affects over 18 million people annually worldwide.
The inability to culture and investigate the agent that causes syphilis in a laboratory setting has been one obstacle that has hampered researchers studying the disease for decades.
“A reliable system for propagating the disease-causing agent in vitro or in a laboratory setting was produced through the incredible efforts of our colleagues and collaborators. According to Brandon Jutras, the project’s principal investigator, an assistant professor of biochemistry in the College of Agriculture and Life Sciences, affiliated faculty of the Fralin Life Sciences Institute, and the Center for Emerging, Zoonotic, and Arthropod-borne Pathogens, “being able to culture the bacterium opens new doors in terms of understanding it in terms of how it causes disease, ways in which we can prevent infection, and efforts in which we may be able to intervene.”
Researchers at Virginia Tech set out to see if there were any potential treatments that could help the millions of people who get the disease every year.
“The tremendous efforts of our colleagues and collaborators resulted in a reliable system for propagating the disease-causing agent in vitro, or in a laboratory setting. Being able to culture the bacterium opens up new avenues for research into how it causes disease, how we might prevent infection, and how we might be able to intervene.“
Brandon Jutras, the principal investigator of the project,
What the School of Horticulture and Life Sciences specialists found surpassed all assumptions. Not only did they discover an alternative to benzathine penicillin G as a treatment, but they also discovered two antimicrobials that were more effective in treating Treponema pallidum, the organism that causes the disease, in a laboratory setting.
The study was recently published in the NPJ Antimicrobials and Resistance journal.
Because the Food and Drug Administration has already granted approval for these drugs, they are safe for humans, which may speed up their distribution.
Kathryn Hayes, the lead author and Ph.D. candidate in Virginia Tech’s Translational Biology, Medicine, and Health program, stated, “It’s a disease for which we have very few therapeutic options.” Without an in vitro culture system, we would not have been able to conduct the first large-scale drug screening for syphilis treatment alternatives.
Now, directly inquire about the researchers’ project from them:
Why did you decide to conduct this study?
Hayes: Infectious diseases and sexual health are two of my favorite subjects. This examination permitted me to join these two interests, as syphilis is an illness that has been around for quite a long time, yet little is known about it because of the trouble of developing the microscopic organisms in a lab setting. A pressing clinical need is more data and research on the disease.
What prodded your advantage in sexual wellbeing?
Hayes: My own strange personality and how disproportionally influenced the eccentric local area is by physically communicated sicknesses roused me. The second is the stigma associated with sexually transmitted diseases (STIs). People will talk about getting the flu or COVID-19, but they won’t say they have syphilis. The way people talk about sexual health, particularly STIs, has changed, and the significance of this research has continued to be emphasized.
In a laboratory setting, the researchers Kathryn Hayes and Brandon Jutras discovered two antimicrobials that were more effective in treating the syphilis agent Treponema pallidum. Max Esterhuizen took this picture for Virginia Tech.
A year and 100 days Can you talk about how you cultured syphilis?
Hayes: The explanation for why it is so difficult is that the microorganisms require extremely severe microaerophilic conditions — a low oxygen climate — which, for this situation, implies precisely 1.5 percent oxygen. We have an incubator that keeps that exact percentage by forcing out excess oxygen with nitrogen. The day preceding my culture, I take a strong mammalian cell line and put it onto customary plates since they actually need a co-culture to help with development. I need to make new media for my way of life.
We have a few components that I make quarterly, and then I have to mix 12 ingredients every week to make the media, which needs to be balanced overnight in our special incubator.
It took at least two hours of preparation the day before, and depending on the number of bacteria in the culture, anywhere from three to seven hours on the day of. One hundred and one days have passed since the beginning of cultivation last week.
How could you direct the medication screening?
Jutras: We started with two tetracyclines, which belong to a different class of antibiotics and served as a cross-comparison. We also used nearly 100 antibiotics from one class. To get a first idea of how effective the antibiotics were at preventing growth, we incubated the bacteria with them at a very low concentration (five nanomolar).
After that, we retested the top 25% of compounds to ensure the accuracy of our analytical techniques.
Advanced microscopy techniques and antibiotic treatment were used to further investigate the top ten percent. We also determined their minimum inhibitory concentrations, which is where we further confirmed that the new candidates Azlocillin and Mezlocillin were more effective than our current standard of care in vitro. In essence, we could observe these compounds in action.
This research may have significant repercussions. What are your next steps in the process?
Jutras: The project posed a significant risk. Addie could have spent a lot of time and done amazing research only to find that nothing worked better than benzathine penicillin G. What’s surprising is that she found a number of better options.
Hayes: I want to investigate modeling the effects of these antibiotics on bacteria. Consequently, investigating the effect of protein-drug interactions on drug efficacy That’s a very interesting mechanistic step, in my opinion, because once you know what the bacteria are doing on a molecular level, you can make compounds that are very similar but slightly different to make treatments that work better.
Provided by Virginia Tech
