The emergence in recent years of antibiotic-resistant bacterial strains has made the treatment of many types of infection more difficult. As a result, researchers are striving to develop more innovative ways to treat what have been routine maladies. A new study of the infection route of uropathogenic Escherichia coli (UPEC), the bacterium most commonly responsible for urinary tract infections (UTIs), does just that by building on a more detailed understanding of bladder physiology.

There are nearly one hundred million UTIs in the world every year, the vast majority of which are caused by UPEC. Perhaps even more troubling, one in four women who are treated for UTIs with antibiotics have a recurrent infection within six months. This result, coupled with the increasing impotence of many antibiotics, is an uncomfortable prospect for many patients and doctors.

Brian L. Bishop of Duke University Medical Center (Durham, NC) decided to investigate the underlying mechanism of UPEC invasion of the bladder. UPEC invasion is contingent on the bacteria attaching themselves to plaques of proteins in the bladder epithelium called uroplakins. These plaques form initially as discoidal vesicles inside the bladder cells that later embed in the cells' apical surface by exocytosis. Prior work by other researchers on the protozoan Trypanosoma cruzi has demonstrated that infection with this parasite is often mediated by secretory lysosomes, membrane-bound cellular compartments similar to the discoidal vesicles of the bladder cells. Bishop and his colleagues reasoned that UPEC invasion and recurrence might be aided by a similar mechanism.

To test this theory, Bishop looked at mice that had been infected with UPEC and found that the bacteria colocalized with molecular markers for the discoidal vesicles (Nat. Med., April). Essentially, their findings revealed that the bacteria enter the bladder cells by invading membrane invaginations produced as the discoidal vesicles fuse with the apical membrane to form the plaques. The bacteria themselves end up shielded within discoidal vesicles inside the bladder cells.

Based on their findings, the researchers proposed a potential UTI treatment: taking advantage of the fact that exocytosis of the vesicles can be induced by an increase in the cellular concentration of cyclic adenosine monophosphate (cAMP), Bishop and his coworkers treated UPEC-infected mice with forskolin, a molecule long recognized to increase cAMP concentrations. This treatment successfully eliminated the mouse UTIs. Forskolin is already used to help treat asthma, glaucoma, and other diseases; researchers hope that forskolin treatment of UTIs will augment antibiotic treatment in humans as well.