How bacteria nestle in

bacteria
Using the protein FimH (yellow/red) the bacterial pathogen E. coli (grey) attaches to cell surfaces of the urinary tract. (Illustration: Maximilian Sauer / ETH Zurich)

Nearly every second woman suffers from a bladder infection at some point in her life. Researchers from ETH Zurich and the University of Basel have now discovered how the intestinal bacterium E. coli attaches itself so successfully to the surface of the urinary tract.

Many women have already experienced how painful a bladder infection can be: a burning pain during urination and a constant urge to urinate are the typical symptoms. The main cause of recurrent urinary tract infections is a bacterium found in the normal flora of the intestine, Escherichia coli. The bacteria enter the urinary tract, attach to the surface and cause inflammation. The teams of Rudolf Glockshuber, Professor at the Institute of Molecular Biology and Biophysics at ETH Zurich, along with Timm Maier and Beat Ernst, Professors at the University of Basel, have now discovered how bacteria adhere to the urinary tract under urine flow via the protein FimH and subsequently travel up the urethra.

Bacterium adheres with FimH

The pathogen has long, hairlike appendages with the protein FimH at its tip, forming a tiny hook. This protein, which adheres to sugar structures on the cell surface, has a special property: It binds more tightly to the cell surface of the urinary tract the more it is pulled. As strong tensile forces develop during urination, FimH can protect the bacterium from being flushed out.

“Through the combination of several biophysical and biochemical methods, we have been able to elucidate the binding behavior of FimH in more detail than ever before”, says Glockshuber. In their study, the scientists have demonstrated how mechanical forces control the binding strength of FimH. “The protein FimH is composed of two parts, of which the second non-sugar binding part regulates how tightly the first part binds to the sugar molecule“, explains Maier. “When the force of the urine stream pulls apart the two protein domains, the sugar binding site snaps shut. However, when the tensile force subsides, the binding pocket reopens. Now the bacteria can detach and swim upstream the urethra.”

Drugs against FimH to combat infections

Urinary tract infections are the second most common reason for prescribing antibiotics. Yet, in times of increasing antibiotic resistance, the focus moves increasingly to finding alternative forms of treatment. For the prevention and therapy of E. coli infections, drugs that could prevent the initial FimH attachment of the bacteria to the urinary tract could prove to be a suitable alternative, as this would make the use of antibiotics often unnecessary. This opens up the possibility of reducing the use of antibiotics and thus preventing the further development of resistance.

This article is based on a press release by the University of Basel.

References

Sauer MM, Jakob RP, Eras J, Baday S, Eriş D, Navarra G, Bernèche S, Ernst B, Maier T, Glockshuber R: Catch-bond mechanism of the bacterial adhesin FimH. Nature Communications, 7 March 2016, doi: 10.1038/ncomms10738