CHICAGO, March 8 (Xinhua) -- U.S. researchers have found a way to treat urinary tract infections (UTIs) without using antibiotics: by blocking the bacteria E. coli from adhering to the mice's urinary tracts, the infection can be treated.
Previous research found that E. coli latches onto sugars on the surface of the bladder with long, hairlike structures called pili to cause UTIs.
Researchers at Washington University School of Medicine in St. Louis created mannosides, modified forms of a sugar called mannose that the bacteria favor over typical sugars on the bladder wall. When mice with UTIs were given the mannosides, the E. coli in their bladders grabbed hold of those molecules and were swept away.
Recently, the researchers found that E. coli also can latch onto galactose, another sugar molecule found on urinary tissues. They then design and screen modified forms of galactose known as galactosides to find versions that attach firmly to the adhesive proteins at the end of the bacteria' s pili.
Using X-ray snapshots of galactosides bound to the adhesive protein as a guide, the researchers synthesized even stickier versions of these molecules.
Then, they pitted each new galactoside against galactose in a competition to see which attached best to the bacterial protein. Galactosides that outcompete galactose may be able to serve as decoys, tricking bacteria into catching hold of a floating galactoside instead of a urinary tract-anchored galactose.
To study the effect, the researchers injected E. coli into the bladders of mice and then gave the mice either the galactoside or a placebo. The numbers of bacteria in the bladders and kidneys of mice given the galactoside dropped by up to a hundredfold.
When mice were simultaneously treated with a mannoside and the galactoside, the bacteria in their bladders dropped a thousand-fold, and the bacteria in their kidneys were nearly eradicated.
"We showed that we can administer two different inhibitors and see a synergistic therapeutic effect," said Vasilios Kalas, the first author and a PhD student at the university. "The data suggest that both types of pili play a role in attachment during infection."
The pilus that attaches to mannose plays a bigger role in the bladder, while the pilus that recognizes galactose seems to be more important in the kidneys. Foiling the bacteria' s attempts to grasp both sugars could target both uncomplicated and serious bladder and kidney infections.
Unlike antibiotics, a drug that undermines the bacteria' s ability to stay in the body is less likely to drive resistance because it would not force bacteria to die or evolve resistance in order to survive, the researchers said.
"We're not killing them, we're just helping flush them out of certain environments where they can do damage," Kalas said.
The researchers also demonstrated that the galactoside prevented the bacteria's adhesive protein from sticking to human kidney tissue.
Further work is needed to show that galactoside is not toxic and can be absorbed into the circulation when taken by mouth before it can enter human trials.
Half of all women will experience the pain and burning of a UTI at some point in their lives, and bacteria E. coli cause 80 percent of UTIs. Sometimes the bacteria travel to the kidneys, causing back pain and fever. In rare cases, they spread to the blood, a potentially lethal complication.
"This is a new way of approaching the problem of antibiotic resistance," said co-senior author Scott J. Hultgren, professor of molecular microbiology at Washington University in St. Louis.
The study was published earlier this week in Proceedings of the National Academy of Sciences.
