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Antibiotic Alternative Treats Urinary Infection in Mice

Prevents bacteria from attaching to bladder

A mannoside drug proved more effective than antibiotics in mice with urinary tract infections, according to lead study author Corinne Cusumano.
A mannoside drug proved more effective than antibiotics in mice with urinary tract infections, according to lead study author Corinne Cusumano.

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Researchers have a new approach for treating urinary tract infections, a painful condition which can often be treated successfully with antibiotics. But many times, the infection is caused by strains of bacteria that are resistant to the drugs.

This new approach may bypass the resistance issue, according to a study published in Science Translational Medicine.

When a urinary tract infection begins, the bacteria attaches, or binds, to the bladder. It does this by clinging to molecular receptors on a sugar called mannose, found normally on the inner surface of the bladder.

James Janetka of Washington University in Saint Louis and his team devised chemicals called mannosides that mimic the mannose and act as a kind of decoy for the bacteria. The idea is that if the bacteria attach to the mannoside, they won't be able to attach to the mannose on the bladder.

"Most antibiotics kill the bacteria," Janetka says. "That's what we call cytotoxics. In our case, our compounds are not cytotoxic. Our compounds actually block this binding of the bacteria to the bladder cells, so that the body's own immune system can clear the bacteria normally."

To test the concept, laboratory mice with urinary tract infections were given a mannoside drug, called "compound 6." Lead author Corinne Cusumano says that in the mice, the mannoside was more effective than antibiotics.

"And six hours after we fed them the mannoside, we looked at the number of bacteria in their bladders," she says. "And we saw that there was a significant reduction in the amount of bacteria in the bladder. And most noticeably, this is actually quicker than the traditional antibiotics."

As well as clearing infection, mannoside given in advance prevented infection, presumably because the bacteria couldn't bind to the bladder surface and infect the tissue.

Janetka says that because of the way they work, the mannoside compounds should not promote the development of resistance in the bacteria, and they should be effective against strains that are hard to treat with current drugs.

"And one of the very exciting things in the paper that we all are quite excited about is that the compounds even work against antibiotic-resistant bacteria."

Janetka says in a best case scenario, clinical trials in humans could begin in a year or so.

He says the same principle - of interrupting the binding process - may also be effective against other kinds of infections.

"And so we can use the same exact technology that we've developed to design inhibitors, based on natural sugars again, that could be effective against many other types of bacteria. So this is just the beginning, in our mind."

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