Molecular research may change management of UTIs


Ongoing research into the pathogenesis of recurrent urinary tract infections is fundamentally changing how scientists view this common problem and may some day alter how clinicians manage it. The research, led by Scott Hultgren, PhD, of the University of Washington in St. Louis, describes a developmental process whereby uropathogenic Escherichia coli invade the superficial epithelial cells of the bladder and contribute to recurrent UTIs.

Dr. Hultgren's model challenges the long-held assumption that the urine is a surrogate for the urinary tract, and that findings on urine culture are appropriate for determining a course of antimicrobial treatment.

"This model suggests that's not always true-that you can have sterile urine in a positive bladder. That leads to different ways of thinking in terms of diagnosis and treatment of UTIs," said Anthony J. Schaeffer, MD, professor and chairman of urology at Northwestern University, Chicago, who called the finding a "major observation."

Four stages In the research, conducted in a mouse model, Dr. Hultgren and colleagues used time-lapsed videomicroscopy to show E coli's infectious process occurring in four developmental stages (Proc Natl Acad Sci USA 2004; 101:1333-8).

In the first stage, bacteria enter bladder cells and quickly begin to replicate. In the second stage, they decrease their size and replication rate and begin to form an intracellular bacterial community (IBC), a pod-like structure. In the third stage, bacteria begin to break free from the IBC and escape from the cell into the bladder lumen. In the fourth stage, pod formation continues, but some bacteria from the dispersed IBC become filaments, which may help them evade the immune system and start new infections both in the urinary tract of their hosts and in new hosts.

Importantly, the videos also showed that groups of E coli occasionally shift into a quiescent state.

"We don't actually know when this happens, but at some point, that's all you see-small numbers of bacteria inside the cells no longer replicating," Dr. Hultgren, professor of molecular microbiology at Washington University, said in a news re-lease.

"They've entered this quiescent state and are presumably no longer causing any symptoms, and the question is whether that quiescent reservoir can now provide seeds for recurrent infections."

Clinical implications The molecular research potentially has valuable clinical implications. Some 50% of all women will experience a UTI during the course of their lives, and recurrent UTIs affect 20% to 40% of these patients. E coli is responsible for an estimated 90% of all UTIs.

"If you have a woman with recurring UTIs, you may want to consider treating her with more intracellular-directed therapies or for longer than 3 days," Dr. Schaeffer said in interpreting the research's long-term implications.

"The old model was that recurring infections were from the outside in and each time were a new event from the gut. This suggests, in some cases anyway, it may be persistence within the bladder."

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