New insights into cystitis may suggest new antibiotic approaches

Insights by an international group of researchers into how Escherichia coli bacteria form the thread-like structures called pili that fasten to the bladder wall to cause cystitis could lead to development of new antibiotics to treat urinary tract infections, according to a study published online in Nature (2011;474[7349]:49-53).

Researchers from the VIB Department for Structural Biology, Vrije Universiteit Brussels, and the Institute of Structural and Molecular Biology, University of London, have for the first time described and successfully imaged the complex process by which uropathogenic E coli form type 1 pili. These pili, or fimbriae, enable the bacteria to adhere to the epithelial cells of the bladder, causing infection.

Using X-ray diffraction the researchers determined that type 1 pili comprise 4 different subentities and are assembled by a mechanism known as the chaperone/usher biosynthesis route. The subunits, bound to chaperone complexes, dock to an usher “plug” that facilitates formation of the pilus.

Detailed knowledge of how type 1 pili form can help to develop drugs to block their biosynthesis and inhibit the ability of E coli to attach to the bladder wall. New antibiotics are needed to replace the current generation, which are losing their potency against E coli, the cause of about 80% of urinary tract infections and a frequent cause of hospital-acquired infections in catheterized patients.

Because bacteria other than E coli use a similar attachment mechanism, the findings of this study also may help combat infections such as food poisoning and traveler’s diarrhea.