Answering a "Burning" Question: How do UTI-causing Bacteria Stick to Bladder Cells?

In news that may shake the cranberry juice industry to its core, new atomic-level "snapshots" reveal how bacteria such as E. coli produce and secrete sticky appendages called pili, which help the microbes attach to and infect human bladder cells.

These crystal structures -- produced at the National Synchrotron Light Source (NSLS) at Brookhaven Lab and the European Synchrotron Radiation Facility in Grenoble, France -- unravel a complex choreography of protein-protein interactions that will aid in the design of new antibacterial drugs. Finding ways to interfere with pili formation could help thwart urinary tract infections, which affect millions of women and men around the world each year.

Two teams of scientists -- one at Brookhaven and Stony Brook University, and another at Washington University School of Medicine and University College London -- used a range of imaging techniques and computer modeling to produce the most complete picture yet of the pore-like transporter protein complex in the act of secreting sticky-ended pili. The research reveals two binding sites for pili subunits on this transporter protein, and details of how these sites work together to recruit, assemble, and transport pili components from the microbe cell's interior to its outer surface.

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The bacterial protein transport channel in its resting closed state (green) and the activated open state (blue). The channel is sealed by a plug structure that is shown in red. Note the change of the channel shape from oval to near circular and displacement of the plug when open. Some parts of the protein molecule are omitted for simplicity.

Blocking or removing either of these two binding sites may be a way to inhibit pilus formation -- an idea already being explored in new drug-development investigations.

The findings were published online in Nature on June 2.

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