Five-year Project Seeks New Weapons Against Drug-resistant Bacteria

Lethal lettuce successful Missouri. Murderous onions successful Colorado. To biochemists astatine nan University of Oklahoma, these aren't conscionable headlines – they're warnings of nan risks posed by drug-resistant germs and nan quality costs of inaction.

Treatment of chronic conditions and galore surgeries requires antibiotics. When germs go resistant to antibiotics and different drugs, galore of our aesculapian advances will besides fail."

Helen Zgurskaya, George Lynn Cross Research Professor, OU Department of Chemistry and Biochemistry

Zgurskaya and Valentin Rybenkov, an OU professor of biochemistry, are starring a five-year, $5.3 cardinal task funded by nan National Institute of Allergy and Infectious Diseases to guarantee that doesn't happen. They purpose to find caller ways to present lifesaving narcotics straight into resistant pathogens.

The activity is essential. Without caller medicines, experts foretell that drug-resistant germs could termination arsenic galore arsenic 2 cardinal group annually by 2050.

"We usually unrecorded together pinch bacteria; we dangle connected them for gut wellness and immunity," Rybenkov said. "We besides person ways to take sides against harmful bacteria, if necessary. But occasionally our defenses fail. When this happens and they turn faster than they're killed by our immune system, we request antibiotics."

Unfortunately, bacterial guidance to nan astir communal antibiotics is expanding quickly worldwide. In October 2025, nan World Health Organization reported that antibiotic resistance has been increasing by arsenic overmuch arsenic 15% annually, and that arsenic galore arsenic 1 successful 6 bacterial infections are resistant. In Southeast Asia and nan eastbound Mediterranean, it's person to 1 in 3.

In nan hunt for remedies, Zgurskaya and Rybenkov person zeroed successful connected a people of pathogenic germs called gram-negative germs (GNB), which person evolved elaborate methods to protect their compartment interiors from intruders, including antibiotics.

Unlike gram-positive bacteria, which person 1 compartment membrane, GNB person 2 membranes, including a robust outer wall. Resistant germs besides person a stronger "efflux" system – protein pumps designed to purge toxic substances from nan cell's interior. These defenses make it difficult for existent classes of narcotics to do their work.

To find holes successful GNB defenses, Zgurskaya and Rybenkov are testing nan permeation properties of astir 2,000 chemicals and compounds against hundreds of efflux pump variants to place candidates that could gaffe done nan membranes of drug-resistant pathogens, including P. aeruginosa, E. coli, K. pneumoniae and A. baumannii. Once an first atlas of viable compounds is created, nan researchers scheme to grow their activity to study moreover much chemicals.

They're besides studying really macromolecule pumps activity astatine nan molecular level successful a bid to place caller avoidance strategies.

"Think of a vessel pinch a mini hole," Zgurskaya said. "Without involution it will sink, slow but surely. But if nan vessel has a h2o pump, it removes immoderate accumulates. It's a akin system successful gram-negative bacteria. Our job, arsenic researchers, is to find a measurement to create a spread and move disconnected nan pump."

With nan thief of instrumentality learning, laboratory results will beryllium tested against an moreover bigger room of chemicals – "hundreds of thousands," Zgurskaya said – to look for patterns and relationships that mightiness constituent to new, much effective therapeutics.

"There is nary easy measurement to foretell what benignant of molecule tin get done a compartment membrane," Rybenkov said. "Artificial intelligence helps america navigate nan data." 

Overuse of antibiotics is often cited arsenic nan starring origin of bacterial resistance, but that's only portion of nan story, Rybenkov said. "Bacteria want to spread; it's a earthy process," he said. "We dangle connected germs for our measurement of life, but immoderate germs don't for illustration us. To them, we're conscionable food."

The OU researchers are collaborating connected nan task pinch Paolo Ruggerone, a professor successful nan Department of Physics astatine nan University of Cagliari, Italy; John Walker, an subordinate professor of medicine science and physiology astatine Saint Louis University; and ArrePath, a drug-discovery patient based successful Princeton, New Jersey.