Researchers present insights into the search for new antibiotics

A collaborative research group from the University of Oklahoma, Memorial Sloan Kettering Cancer Center, and Merck & Co. published an opinion piece in the journal, Chemical biology of nature, which addresses the gap in the discovery of new antibiotics.

“The continued emergence of antibiotic-resistant bacteria and our inability to develop new antibiotics to fight them are two of the most serious health problems we face,” said Tomás Díaz de la Rubia, Vice President of the OU for Research and Partnerships . “The OU team is working hard to develop solutions to these major challenges and their opinion piece helps bring visibility and attention to these issues at a time when it is most needed.”

The research team is made up of OU researchers Helen Zgurskaya, Valentin Rybenkov and Adam Duerfeldt, all in the Department of Chemistry and Biochemistry, College of Arts and Sciences, with researchers from Memorial Sloan Kettering Cancer Center, led by Derek Tan, and researchers of Merck & Co.

“The rapid spread of antibiotic-resistant bacteria in clinics challenges our modern medicine, and traditional approaches to antibiotic discovery fail to generate new drugs needed to treat antibiotic-resistant infections,” Zgurskaya said. “The current COVID-19 pandemic further amplifies this problem because patients in intensive care units are particularly vulnerable to such infections … (our) team is working on developing new tools to guide the discovery and optimization of new antibacterial agents.

Zgurskaya adds that the increasing frequency of antibiotic resistance has created a significant health challenge and will progressively worsen without innovative solutions.

“In particular, Gram-negative pathogens present biological and chemical challenges that hinder the discovery of new antibacterial drugs,” Zgurskaya said. “As a result of these challenges, intensive screening campaigns have yielded little success, highlighting the need for novel approaches to identify regions of the chemical space that are specifically relevant for antibacterial drug discovery.”

In the article, the research team provides an overview of emerging insights into this problem and outlines a general approach for researchers and scientists to address it.

“The overall goal is to develop robust cheminformatics tools to predict Gram-negative permeation and efflux, which can then be used to guide pharmaceutical chemistry campaigns and the design of antibacterial discovery libraries,” Zgurskaya said.