The gram-negative cell envelope and the pathways of drug flows across it. Photo credits: Zhao, S., Adamiak, JW, Bonifay, V. et al. Definition of a new chemical space for drug penetration into gram-negative bacteria. Nat Chem Biol 16, 1293- 1302 (2020). DOI 10.1038 / s41589-020-00674-6
Researchers from the University of Oklahoma published an opinion piece in the journal Natural chemical biology This closes the gap in the discovery of new antibiotics.
“The persistent emergence of antibiotic-resistant bacteria and our inability to develop new antibiotics to fight them represent two of the worst health problems we face,” said Tomás Díaz de la Rubia, vice president of research and partnerships OU. “The OU team is working hard to find solutions to these major challenges. The opinion piece helps bring these issues to the fore at a time when they are most needed.”
The research team consists of OU researchers Helen Zgurskaya, Valentin Rybenkov, and Adam Duerfeldt, all in the Department of Chemistry and Biochemistry at the College of Arts and Sciences, with researchers from the Memorial Sloan Kettering Cancer Center led by Derek Tan, and corporate researchers from Merck & Co.
Comprehensive approach to the development of cheminformatic tools to predict the accumulation of gram-negative bacterial compounds. Photo credit: Justyna Adamiak
“The rapid spread of antibiotic-resistant bacteria in clinics is challenging our modern medicine, and traditional approaches to antibiotic discovery are not leading to new drugs that are needed to treat antibiotic-resistant infections,” said Zgurskaya. “The current COVID-19 A pandemic exacerbates this problem as ICU patients are particularly vulnerable to such infections. (Our) team is working on the development of new tools to control the discovery and optimization of new antibacterial agents. ”
Zgurskaya adds that the increasing incidence of antibiotic resistance is a significant health care challenge and will continue to deteriorate without innovative solutions.
“Gram-negative pathogens in particular pose both biological and chemical challenges that hinder the discovery of new antibacterial drugs,” said Zgurskaya. “As a result of these challenges, intense screening campaigns have been unsuccessful, highlighting the need for new approaches to identify regions of chemical space that are specifically relevant to antibacterial drug discovery.”
In the article, the research team provides an overview of new evidence on the problem and outlines a general approach for researchers and scientists to address this problem.
“The overall goal is to develop robust cheminformatic tools for predicting gram-negative permeation and effluent that can then be used as a guide for medicinal chemistry campaigns and antibacterial discovery library design,” said Zgurskaya.
Reference: “Definition of a new chemical space for the penetration of drugs into Gram-negative bacteria” by Shibin Zhao, Justyna W. Adamiak, Vincent Bonifay, Jitender Mehla, Helen I. Zgurskaya and Derek S. Tan, November 16, 2020, Natural chemical biology.
DOI: 10.1038 / s41589-020-00674-6
The research received funding from the US Department of Health and the National Institutes of Health. The article “Defining a new chemical space for drug penetration into gram-negative bacteria” is in the November 2020 issue of the journal ” Natural chemical biology.
