When you鈥檙e fighting a urinary tract infection, you might not want to dwell on the details of what鈥檚 going on down there. But there鈥檚 been a longstanding mystery about these common infections 鈥� how do the offending bugs manage to climb up into your bladder without being flushed out when you pee?
The answer is that they can grip tightly to the body鈥檚 cells whenever they feel the force of urine flowing past. When urination stops, the mechanism releases, and the bacteria carry on moving onwards and upwards further into your body.
The discovery is useful because it could mean urinary tract infections could be treated without antibiotics. Drugs that target this machinery would not kill the microbes, just stop them from hanging on, so they should be less likely to provoke resistance, says of charity Antibiotic Research UK, who was not involved in the study. 鈥淚 suspect this approach will point us in the direction of powerful medicines.鈥�
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Grappling hook
About half of all women experience urinary tract infections at some point in their lives, and men can get them too. They are usually caused by Escherichia coli from faeces reaching the urethra, the tube that connects the bladder to the outside of the body.
We already knew that E. coli can grip to human cells using hair-like appendages that have tiny protein hooks on their tips, but until now no one had worked out the structure of this protein, called FimH, or how it interacts with human cells.
The hooks are made of interlinking chains of FimH, which are difficult to pull apart into separate protein molecules without altering their structure. Now researchers in Switzerland have managed to isolate individual FimH molecules for the first time, allowing them to investigate the protein鈥檚 physical properties.
They found that when FimH is pulled by tensile forces 鈥� as it would be during urination 鈥� the protein responds by gripping tightly to the sugar molecules that coat the surface of human cells. 鈥淭hat makes it hard to flush it out,鈥� says Tim Maier of the University of Basel.
When urination stops and the force disappears, the protein releases its grip, and the bacteria can advance up to the bladder 鈥� a cosy home with a more stable temperature and pH than the urethra 鈥� where it causes cystitis.
A new target
Antibiotics are the best treatment for cystitis, but antimicrobial resistant UTIs are a growing problem. In the UK, antibiotic resistance is relatively rare, affecting about 2 to 10 per cent of all infections treated with antibiotics. But widespread resistance to has been reported in UTI-causing microbes.
In some countries, resistance in E. coli is so widespread that UTIs are effectively untreatable.
Targeting the bacteria鈥檚 grappling hooks could get around this problem, and the team is that block FimH in animals.
鈥淩esistance could still develop but it would be harder for the bacteria,鈥� says Brown.
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