A number of drugs already approved to treat parasitic infections, cancers, infertility and other conditions also show promise as antibiotic agents against staph and tuberculosis infections, according to a new study by University of Illinois chemists and collaborators. Because these agents act against multiple targets within the bacteria, it may be harder for bacteria to develop resistance.
The new study, led by Illinois chemistry professor Eric Oldfield, was published in the Proceedings of the National Academy of Sciences.
"There is obviously a huge need for new antibiotics," said Oldfield. "We now have bacteria that are totally drug resistant. Bugs are clever: They can adapt and find ways around the things we develop to kill them. So if we attack them at multiple targets, it's harder for them to make one little change to get around it."
The researchers were interested in finding compounds that sabotage the bacteria's energy production line, shutting down cellular processes within the bacterium. These agents, called uncouplers, are already used to treat parasitic infections. Inspired by clofazimine, a leprosy drug that is now being used to treat tuberculosis, the researchers searched among drugs that are either already available or in development to find uncouplers based on their chemical structures.
"What we found is that a lot of FDA-approved molecules that are in use actually do kill bacteria and also act as uncouplers. We were kind of surprised to find that," Oldfield said. "What's even better is that some of those molecules also inhibit enzymes specific to bacteria, or disrupt the membrane or the cell wall."
Such multitarget drugs could have broader applications against an assortment of infections.
For example, one of the most promising uncouplers the study found was vacquinol, a compound being developed to treat glioblastoma, a form of brain cancer. They found that vacquinol inhibits a key enzyme involved in virulence in tuberculosis bacteria, in addition to its uncoupling properties.
The researchers then searched for other compounds with similar structures to vacquinol and found compounds that were potent antibiotics against tuberculosis and Staphylococcus aureus.
"It's a new approach to antibiotics, targeting enzymes together with bacterial energy production," Oldfield said.
Next, Oldfield hopes to develop compounds that are metabolized into uncouplers inside the bacterial cell, further reducing cross-reactivity with human cells and making it more difficult for bacteria to develop resistance. For example, certain heartburn drugs are metabolized within the cell into a compound that acts against tuberculosis.
"The whole idea is that it's possible that some of these compounds that are FDA-approved will work. You can screen a million chemicals to find a new compound but in general you have no idea about its toxicology, or you can start with something that's known," Oldfield said. "Once you start making derivatives, you'll have to prove they're safe, but there's a greater chance to get something that's safe and effective by starting with an approved drug than if you just go into the chemistry lab and screen unknown compounds."
Source: University of Illinois at Urbana-Champaign
Dear Helpdesk: Working in a Toxic Health Care Environment
March 28th 2024Dear Helpdesk is your steadfast companion, offering life coaching and workplace advice from 2 seasoned IPs for some of your most challenging real-life situations. Let us help you navigate the intersection between work and life, guiding you to navigate the dynamic world of infection prevention with confidence and grace. This article is on handling a toxic health care environment.
Product Locator: Spring and Early Mother's Day Gift Guide for Infection Prevention Personnel
March 27th 2024Whether it's a spring holiday, birthdays, or no reason at all, infection prevention personnel love to give and receive gifts that help at the end of a stressful day. Infection Control Today® offers some gift ideas for infection prevention personnel and their families.
Catching Up With Vangie Dennis, AORN 2022-2023 President at AORN 2024
March 26th 2024Infection Control Today (ICT) had the privilege of catching up with Vangie Dennis, MSN, RN, CNOR, CMLSO, at the Association of periOperative Registered Nurses' (AORN’s) International Surgical Conference & Expo 2024. As the former president of AORN and an esteemed figure in perioperative services, Vangie Dennis shared insights into her recent endeavors and the exciting new chapter she's embarked upon.
How To Optimize Your Time Management Strategies for the Busy Infection Preventionist
March 25th 2024Is your calendar resembling a chaotic masterpiece of overlapping tasks? Join the club of infection preventionists striving to balance responsibilities. Dive into proven strategies from a fellow infection preventionist to reclaim control of your time, streamline tasks, and boost productivity effectively. This is an IP Lifeline article.