New Drug Candidate Fights
Off More than 300 Drug-Resistant Bacteria
Urinary
tract infections are common, yet are increasingly tough to treat because the
bacteria that cause them are becoming resistant to many antibiotics. Now,
in ACS Central Science, researchers report a new molecule that
inhibits drug-resistant bacteria in lab experiments, as well as in mice with
pneumonia and urinary tract infections.
From:
American Chemical Society
August 10, 2022 -- The researchers say that this
compound, fabimycin, could one day be used to treat challenging infections in
humans.
Gram-negative bacteria are a class of microbes that
infect millions of people worldwide, according to the U.S. Centers for Disease
Control and Prevention, causing conditions such as pneumonia, urinary tract
infections and bloodstream infections. These bacteria are especially difficult
to treat because they have strong defense systems - tough cell walls that keep
most antibiotics out and pumps that efficiently remove those antibiotics that
get inside. The microbes can also mutate to evade multiple drugs. Furthermore,
treatments that do work aren't very specific, eradicating many kinds of
bacteria, including those that are beneficial. So, Paul Hergenrother and
colleagues wanted to design a drug that could infiltrate the defenses of
gram-negative bacteria and treat infections, while leaving other helpful
microbes intact.
The team started with an antibiotic that was active
against gram-positive bacteria and made a series of structural modifications
that they believed would allow it to act against gram-negative strains. One of
the modified compounds, dubbed fabimycin, proved potent against more than 300
drug-resistant clinical isolates, while remaining relatively inactive toward
certain gram-positive pathogens and some typically harmless bacteria that live
in or on the human body. In addition, the new molecule reduced the amount of
drug-resistant bacteria in mice with pneumonia or urinary tract infections to
pre-infection levels or below, performing as well as or better than existing
antibiotics at similar doses. The researchers say the results show that
fabimycin could one day be an effective treatment for stubborn infections.
The authors acknowledge funding from the University
of Illinois, the National Institutes of Health, the National Science
Foundation, the Combating Antibiotic-Resistant Bacteria Biopharmaceutical
Accelerator, Anita and Josh Bekenstein, Biomedical Advanced Research and
Development Authority, Military Infectious Diseases Research Program and the
Roy J. Carver Charitable Trust.
https://www.sciencedaily.com/releases/2022/08/220810105207.htm
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