Global Challenges/Chemistry Solutions

Combating Disease: A non-antibiotic approach for treating urinary tract infections

August 13, 2012

E. coli bacteria
A non-antibiotic approach for treating
urinary tract infections, which are often
caused by E. coli bacteria.

Credit: Centers for Disease Control and Prevention.

Summary

A potential new approach for treating urinary
tract infections (UTIs) — which affect
millions of people annually — without
traditional antibiotics is being reported in
ACS’ Journal of Medicinal Chemistry. It
involves so-called FimH antagonists, which
are non-antibiotic compounds and would
not contribute to the growing problem of
antibiotic resistance bacteria.

Today’s episode describes a potential new approach for treating urinary tract infections (UTIs) without traditional antibiotics. UTI affects millions of people annually and if left untreated can lead to devastating complications like irreversible kidney damages and finally to urosepsis. Urosepsis is an accumulation of poisonous bacteria or their toxins in the blood of the urinary tract. This can lead to complications like damage to organs and even death.

The approach, which involves so-called FimH antagonists, non-antibiotic compounds that would not contribute to the growing problem of antibiotic resistance bacteria, is the topic of a report in ACS’ Journal of Medicinal Chemistry.

Beat Ernst, Ph.D., who is with University of Basel and is the lead author of the paper, notes that antibiotics are the mainstay treatment for UTIs. Bacteria, however, are developing resistance to common antibiotics, with the emergence of “super bugs” that shrug off some of the most powerful new antibiotics. So the scientist and his team decided to try a new approach to this problem. He explains.

“We developed substances that target bacteria virulence factors, keeping them from sticking to the inside of the urinary bladder. Therefore, the microbes are not able to launch an infection. In addition, this new class of antimicrobials is expected to have a reduced potential for the emergence of resistant microbes.”

Ernst and the team explain how they developed anti-adhesion molecules that specifically interfere with the attachment of bacteria to human bladder cells. The most potent of the substances, an indolinylphenyl mannoside, prevented a UTI from developing in mice (stand-ins for humans in this kind of experiment) for more than eight hours. In the study, they gave a very low dose of 25 micrograms per mouse. This reduced the amount of bacteria in the bladder of the animals by almost 10,000 times, which is comparable to the standard antibiotic treatment with ciprofloxacin.

Smart Chemists/Innovative Thinking

Smart chemists. Innovative thinking. That’s the key to solving global challenges of the 21st Century. Please check out more of our full-length podcasts on wide-ranging issues facing chemistry and science, such as promoting public health, developing new fuels and confronting climate change, at www.acs.org/GlobalChallenges. Today’s podcast was written by Michael Bernstein. I’m Adam Dylewski at the American Chemical Society in Washington.

Beat Ernst, Ph.D.
Beat Ernst, Ph.D.
Group leader, molecular pharmacy
University of Basel
Basel, Switzerland