ATLANTA—Carbon monoxide can improve the effectiveness of antibiotics, making bacteria more sensitive to antibiotic medication, according to a study led by Georgia State University.
Researchers paired carbon monoxide with the antibiotic metronidazole and found carbon monoxide enhanced the efficacy of the antibiotic against H. pylori, a type of bacteria that infects the stomach and causes peptic ulcers. The findings are published in the journal Organic Letters.
“We found that if you administer carbon monoxide together with an antibiotic called metronidazole, it can sensitize bacteria toward the same antibiotic by 25-fold,” said Dr. Binghe Wang, Regents’ Professor of Chemistry and director of the Center for Diagnostics & Therapeutics at Georgia State and a Georgia Research Alliance Eminent Scholar in Drug Discovery. “It makes the bacteria much, much more sensitive to the antibiotic.
“We always hear about the discussions of drug resistance. When we have drug resistance, it’s not because these bacteria will not respond to antibiotics anymore. Most of the time, it means there is decreased sensitivity. If you can resensitize bacteria or sensitize them, then that would allow you to either use a smaller amount of antibiotic or use the same amount that would kill many, many more bacteria.”
Carbon monoxide is infamous for its toxicity at high concentrations, but it also has promising potential as a medical gas. Produced naturally in the human body, carbon monoxide is essential for survival and plays an important role in reducing inflammation, promoting cell proliferation and regulating cellular immune response to pathogens. Studies have found carbon monoxide has antimicrobial effects.
In this study, the researchers developed a prodrug system that releases three components: carbon monoxide, an antibiotic (metronidazole) and a fluorescent molecule used to monitor the release of carbon monoxide. A prodrug is the precursor of a drug and must undergo a chemical conversion before becoming an active pharmacological agent. This prodrug system has a three-reaction sequence and becomes active when placed in water, which sets the reaction in motion.
They studied H. pylori bacteria in a culture dish and compared the effect of only the antibiotic metronidazole against the bacteria versus the prodrug system with metronidazole and carbon monoxide combined.
Co-authors of the study include Ladie Kimberly C. De La Cruz, Zhixiang Pan, Bingchen Yu and Xingyue Ji of Georgia State and Stéphane L. Benoit and Robert J. Maier of the University of Georgia.
To read the study, visit https://pubs.acs.org/doi/abs/10.1021/acs.orglett.7b03348.
Dr. Binghe Wang
Director of the Center for Diagnostics & Therapeutics,
Regents’ Professor of Chemistry
Department of Chemistry
Dr. Binghe Wang is a Regents’ Professor of Chemistry, Georgia Research Alliance Eminent Scholar in Drug Discovery and Georgia Cancer Coalition Distinguished Cancer Scholar. He also serves as Associate Dean for Research, Innovation, and Graduate Studies in the College of Arts and Sciences. Wang has published over 270 scientific papers and trained a large number of graduate and undergraduate students as well as postdoctoral fellows. His research areas include drug design and drug delivery with an emphasis on new drugs against cancer, infectious diseases and inflammatory conditions as well as new diagnostics for cancer, cardiovascular abnormalities and other diseases.