Tuesday, 24 April 2018

Decoy molecules target E. coli to treat UTI in mice



Researchers have designed sugar molecules that block E. coli bacteria from binding to urinary tissues, allowing the bacteria to be washed out of the urinary tract. The compounds represent a step toward treating UTIs without antibiotics.

The bacteria E. coli cause 80 percent of UTIs, leading to painful, burning urination. The bacteria then sometimes travel to the kidneys, causing back pain and fever. In rare cases, they spread to the blood, a potentially lethal complication.

Often, UTIs can be cleared up with antibiotics, but 10 to 20 percent of cases do not respond to current first-line drugs. Hultgren and his colleagues are working on an alternative that would prevent bacteria from causing disease, which may help reduce dependency on antibiotics.

E. coli's first step in causing UTIs is to latch onto sugars on the surface of the bladder with long, hairlike structures called pili. Hultgren and co-senior author James W. Janetka, PhD, an associate professor of biochemistry and molecular biophysics, previously 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.

Researchers have shown that E. coli also can latch onto galactose, another sugar molecule found on urinary tissues. A drug that undermines the bacteria's ability to stay in the body is less likely to drive resistance because, unlike antibiotics, it would not force bacteria to die or evolve resistance in order to survive, the researchers said.

The researchers also demonstrated that the galactoside prevented the bacteria's adhesive protein from sticking to human kidney tissue.

See:

Vasilios Kalas, Michael E. Hibbing, Amarendar Reddy Maddirala, Ryan Chugani, Jerome S. Pinkner, Laurel K. Mydock-McGrane, Matt S. Conover, James W. Janetka, Scott J. Hultgren. Structure-based discovery of glycomimetic FmlH ligands as inhibitors of bacterial adhesion during urinary tract infection. Proceedings of the National Academy of Sciences, 2018; 201720140 DOI: 10.1073/pnas.1720140115



Posted by Dr. Tim Sandle

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