Most cases of urinary track infections or UTI are caused by Escherichia coli. Found in the normal flora of the intestine and passed through the faeces, these bacteria are able to reach urethra—the tube that connects the bladder to the outside of the body. They are able to advance to the bladder despite intense pressure exerted by urination. It turns out these microbes use hooks to hang on, thus withstanding urinary flow.
Specialists are already aware of the fact that E. coli are able to maintain grip to human cells using hair-like appendages with tiny hooks at the tip made of interlinking chains of protein called FimH. However, the interaction between FimH protein and human cells was initially unclear.
Studying the FimH protein was challenging because it was difficult to separate it from the entire interlinking protein chain without altering its structure. But for the first time, researchers from the University of Basel and the ETH Zurich were able to isolate individual FimH molecules. This allowed them to explore the physical properties of the proteins.
“Through the combination of several biophysical and biochemical methods, we have been able to elucidate the binding behaviour of FimH in more detail than ever before,” said Rudi Glockshuber, one of the researchers and professor Institute of Molecular Biology and Biophysics at the ETH Zurich.
In their paper, researchers explored and explained how the FimH protein works. Accordingly, the protein adheres to sugar molecules that coat the surface of human cells. It also has a special property. When strong tensile force due to pressure from urination pulls FimH, it responds by gripping tightly to the sugar molecule.
In other words, the E. coli bacteria bind more tightly to the cell surface of the urine track the more they are pulled. The FimH protein thereby protects the bacteria from being flushed out.
“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,” said Timm Maier, one of the researchers and professor at the University of Basel. “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.”
When the pressure from urination stops, the FimH protein releases its grip from the cell surface. The bacteria then travel upward to the bladder—a suitable environment for E. coli proliferation due to stable temperature and pH. Bacterial proliferation in the bladder result in an inflammation called cystitis.
Cystitis or bladder infection can be painful and annoying. Individuals who suffer from cystitis typically experience a burning sensation while urinating and a strong, persistent urge to urinate. Some experience blood in the urine, pelvic discomfort, and a low-grade fever, among others. If left untreated, the infection can become a more serious health problem if it spreads to the kidneys.
Nonetheless, findings from the aforementioned study open new ways for treating UTI. Take note that this disease is one of the most common reasons for prescribing antibiotics. However, because of increasing antibiotic resistance, researchers are finding alternative forms of treatment. It is also worth mentioning that the prevalence of E. coli in other countries has rendered UTI almost untreatable due to the emergence of antibiotic-resistant strains.
A drug that could prevent the mechanism of FimH protein could be an effective prevention and therapy for UTI caused by the E. coli bacteria. This drug could be a viable alternative to antibiotics. Thus, the drug could also reduce the prevalence of antibiotic-resistant bacterial strains.
Further details of the study of Glockshuber et al are in the article “Catch-bond mechanism of the bacterial adhesin FimH” published in March 2016 in the journal Nature Communications. Photo credit: M. M. Sauer/ ETH Zurich