New treatment reduces E. coli, may offer alternative to antibiotics
Staff Writer |
Urinary tract infections (UTIs) are among the most common infections, and they tend to come back again and again, even when treated. Most UTIs are caused by E. coli that live in the gut and spread to the urinary tract.
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A new study from Washington University School of Medicine in St. Louis has found that a molecular decoy can target and reduce these UTI-causing bacteria in the gut.
With a smaller pool of disease-causing bacteria in the gut, according to the researchers, the risk of having a UTI goes down.
"The ultimate goal of our research is to help patients manage and prevent the common problem of recurrent urinary tract infections while at the same time helping to address the worldwide crisis of antimicrobial resistance," said Scott J. Hultgren, PhD, the Helen L. Stoever Professor of Molecular Microbiology and the study's senior author.
"This compound may provide a way to treat UTIs without the use of antibiotics."
Close to 100 million people worldwide acquire UTIs each year, and despite antibiotic treatment, about a quarter develop another such infection within six months. UTIs cause painful, burning urination and the frequent urge to urinate.
In serious cases, the infection can spread to the kidneys and then the bloodstream, where it can become life-threatening.
Most UTIs are caused by E. coli that live harmlessly in the gut. However, when shed in the feces, the bacteria can spread to the opening of the urinary tract and up to the bladder, where they can cause problems.
Conventional wisdom holds that UTIs recur frequently because bacterial populations from the gut are continually re-seeding the urinary tract with disease-causing bacteria.
Hultgren, graduate student Caitlin Spaulding, and colleagues reasoned that if they could reduce the number of dangerous E. coli in the gut, they could reduce the likelihood of developing a UTI and possibly prevent some recurrent infections.
First, the researchers identified genes that E. coli need to survive in the gut. One set of genes coded for a kind of pilus, a hairlike appendage on the surface of E. coli that allows the bacteria to stick to tissues, like molecular velcro. Without this pilus, the bacteria fail to thrive in the gut.
Earlier studies found that the identified pilus attaches to a sugar called mannose that is found on the surface of the bladder. Grabbing hold of mannose receptors on the bladder with the pilus allows the bacteria to avoid being swept away when a person urinates. Bacteria that lack this pilus are unable to cause UTIs in mice.
Previously, Hultgren and co-author, James W. Janetka, PhD, an associate professor of biochemistry and molecular biophysics at Washington University, chemically modified mannose to create a group of molecules, called mannosides, that are similar to mannose but changed in a way that the bacteria latch onto them more tightly with their pili.
Unlike mannose receptors, though, these mannosides are not attached to the bladder wall, so bacteria that take hold of mannosides instead of mannose receptors are flushed out with urine.
Since the researchers found that this same pilus also allows the bacteria to bind in the gut, they reasoned that mannoside treatment could reduce the number of E. coli in the gut and perhaps prevent the spread of the bacteria to the bladder.
To test this idea, they introduced a disease-causing strain of E. coli into the bladders and guts of mice to mirror the pattern seen in people. In women with UTIs, the same bacteria that cause problems in the bladder usually also are found living in the gut.
The researchers gave the mice three oral doses of mannoside, and then measured the numbers of bacteria in the bladders and guts of the mice after the last dose of mannoside.
They found that the disease-causing bacteria had been almost entirely eliminated from the bladder and reduced a hundredfold in the gut, from 100 million per sample to 1 million. ■