New data offer clues to why some UTIs persist after treatment

Scientists at Washington University School of Medicine in St. Louis have found new clues to why some urinary tract infections recur persistently after multiple rounds of treatment.

Their research, conducted in mice, suggests that the bacteria that cause urinary tract infections take advantage of a cellular waste disposal system that normally helps fight invaders. In a counterintuitive finding, they learned that when the disposal system was disabled, the mice cleared urinary tract infections much more quickly and thoroughly.

"This could be the beginning of a paradigm shift in how we think about the relationship between this waste disposal system, known as autophagy, and disease-causing organisms," said senior author Indira Mysorekar, PhD. "There may be other persistent pathogens that have found ways to exploit autophagy, and that information will be very useful for identifying new treatments."

Data from the new study and earlier results have led Dr. Mysorekar and her colleagues to speculate that Escherichia coli that cause recurrent urinary tract infections may hide in garbage-bin-like compartments within the cells that line the urinary tract.

These compartments, known as autophagosomes, sweep up debris within the cell, including harmful bacteria and worn-out cell parts. Then, they merge with other compartments in the cell that are filled with enzymes that break down the contents of autophagosomes.

"We think, but can’t yet prove, that the bacteria have found a way to block this final step," Dr. Mysorekar said. "This would transform the autophagosome from a death trap into a safe haven where the bacteria can wait, hidden from the immune system, for their next chance to start an infection."

The scientists identified structural changes in urinary tract cells of the mice with Atg16L1 mutations that may help explain their unexpected results. These changes may have made it much more difficult for the bacteria to find and break into autophagosomes, Dr. Mysorekar says.

The altered gene also was associated with changes in the immune system. In the modified mice, E. coli infections in the urinary tract led cells to produce more inflammatory immune factors and prompted additional bacteria-fighting immune cells to come to the site of the infection.

Results from the study were published online in The Proceedings of the National Academy of the Sciences (June 19, 2012).

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