A false-color scanning electron micrograph of the water-borne intestinal parasite Giardia lamblia. Image courtesy of Centers for Disease Control and Prevention.
New More Effective Antimicrobials Might Rise From Old
Findings could have major impact in struggle against evolving drug resistance
By tinkering with their chemical structures, researchers at the University of California, San Diego School of Medicine have essentially re-invented a class of popular antimicrobial drugs, restoring and in some cases, expanding or improving, their effectiveness against drug-resistant pathogens in animal models.
Writing in the October 7 Early Edition of PNAS, Lars Eckmann, MD, professor of medicine, and colleagues describe creating more than 650 new compounds by slightly altering structural elements of metronidazole and other 5-nitromidazoles (5-NI), a half-century-old class of antimicrobial drugs used to combat everything from an ulcer-causing stomach bacterium to a gut-churning protozoan found in contaminated water.
“The basic building blocks of 5-NI drugs are the same for all. We decorated around them, adding extra molecular pieces to change their shapes and sizes,” said Eckmann, who published the paper with colleagues at UC San Diego, The Scripps Research Institute and the Queensland Institute of Medical Research in Australia. The result: The altered shapes changed how many of the new compounds attacked pathogens in animal models, overcoming previous microbial resistance.
The findings could have major ramifications in the on-going struggle against evolving drug resistance by many disease-causing pathogens. The Centers for Disease Control and Prevention recently estimated at least 2 million Americans fall ill to antibiotic-resistant bacteria each year, with at least 23,000 dying as a direct result of those infections. The World Health Organization (WHO) deems antimicrobial resistance to be an escalating global threat to public health.
“Antibiotic resistance is rising for many different pathogens that are threats to health,” said CDC director Tom Frieden, MD, MPH. “If we don’t act now, our medicine cabinet will be empty and we won’t have the antibiotics we need to save lives.”
To be sure, antibiotic drug resistance varies. “It spans the spectrum,” said Eckmann. “We have some disease-causing bugs where the situation is critical, where we’re really at risk of losing the ability to treat any infection. At the other end, some infections are not much impacted at all. It depends upon the particular bug.”