Promising new ways to treat antimicrobial resistance
Medicinal chemists at the University of Florida report results from a study focused on new ways of treating several types of antibiotic-resistant bacteria, advances that may help in the battle against MRSA, tuberculosis and other infectious pathogens, wrote Donovan Baltich for University of Florida Health.
Lead investigator Robert Huigens, PhD, Associate Professor of Medicinal Chemistry in the UF College of Pharmacy and a member of the UF Health Cancer Center, synthesized a new series of more than 20 different halogenated phenazine, or HP, small molecules with his team.
“HP small molecules could lead to critical advances in the treatment of significant infections, including wounds and chronic infections,” he said. The research was the focus of the cover story in the American Chemical Society’s Journal of Medicinal Chemistry.
In their experiments, three of the HP small molecules successfully starved MRSA, or methicillin-resistant Staphylococcus aureus, of iron. MRSA, a superbug that commonly infects open wounds, needs iron from a host to thrive. By taking away their iron source, the HPs can eradicate the infection.
Several HP small molecules inhibited the growth of Mycobacterium tuberculosis, the bacterium responsible for causing tuberculosis. The infectious disease causes more deaths worldwide than any other bacterial pathogen, at 1.5 million each year.
One HP small molecule proved effective in treating two bacteria in an animal study: Staphylococcus aureus and Enterococcus faecalis. S. aureus is a major human pathogen involved in community- and hospital-acquired antibiotic resistant infections. E. faecalis is notorious for causing untreatable foot ulcers in patients who have diabetes. Diabetic extremity ulcers develop in almost 15% of people with diabetes and are a leading cause of hospital admission and amputation among this group of patients.
“This series of compounds is inspired by a marine phenazine antibiotic that we showed has antibacterial activity in our previous work. Synthetic analogues, which we call ‘halogenated phenazines,’ have been further developed using a combination of organic chemistry, microbiology and molecular biology,” Huigens said. “Resistant- and tolerant-bacterial pathogens give rise to numerous problems for patients and our class of compounds aims to fix that.”
