Bladder Cells Use Exocytosis to Fight Urinary Tract Infections

Investigators at Duke University (Durham, NC, USA) and colleagues at the National University of Singapore (Singapore) worked with mice and cultured human bladder cells to study the mechanism used by the bladder to fight off urinary tract infection (UTI).

They reported in the July 19, 2016, online edition of the journal Immunity that infected bladder epithelial cells (BECs) mobilized the exocyst complex, a powerful exporter of subcellular vesicles, to rapidly expel intracellular bacteria back for clearance. In this process, called exocytosis, membrane-bound secretory vesicles are carried to the cell membrane, and their contents (water-soluble molecules such as proteins) are secreted into the extracellular environment. This secretion is possible because the vesicle transiently fuses with the outer cell membrane.

While the investigators had previously reported that expulsion of harmful bacteria was partially mediated by lysosomes, cellular structures that ordinarily degrade waste, this was the first report of bacterial expulsion via exocytosis. In addition, this process was linked to action of the compound Forskolin, which has a strong impact on urinary tract infections, even in the absence of antibiotics. Forskolin activates the enzyme adenylyl cyclase and increases intracellular levels of cAMP, an important second messenger necessary for the proper biological response of cells to hormones and other extracellular signals.

"There is growing interest in identifying new ways to fight UTIs, as bacteria are becoming increasingly resistant to antibiotics," said senior author Dr. Soman Abraham, professor of pathology, immunology, microbiology, and molecular genetics at Duke University. "In the past, we identified a plant extract called Forskolin, which has a strong impact on UTIs, even in the absence of antibiotics. Unfortunately, we did not understand how it worked. These latest findings could provide the key to how the herb effectively combats UTIs. If this link can be established, we could help advance the case for testing the herb and other similar-acting drugs as a potential new treatment for UTIs."

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Duke University
National University of Singapore