The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection

Jun 9 2006

Researchers at Karolinska Institutet in Sweden have succeeded in explaining how the body protects itself against urinary tract infections; with the help of an endogenous antibiotic.

The discovery, which is being published in the prestigious scientific journal Nature Medicine, revolutionises our understanding of how the body defends itself against bacterial attack in the urinary tract.

"Antibiotic-resistant bacteria are a growing problem," explains research leader Professor Annelie Brauner. "As the development of resistance to the body's own antibiotic is very rare, it can be used as an alternative or a complement to conventional antibiotic medication."

Urinary tract infection is currently one of the ten most common reasons for outpatient visits. Up to 60 % of all women develop a urinary tract infection at one time in their life, and of these, 20 % have recurrent problems with it. Children less often have urinary tract infections but when the kidneys are involved up to 40 % get scarring of the kidneys.

It was previously thought that the urinary tract was kept sterile by the flow of urine, which stops bacteria from lodging in the mucus membrane of the urinary tract. However, scientists at the Department of Microbiology, Tumour and Cell Biology have now shown that an endogenous peptide is of critical significance to the prevention of urinary tract infection, a finding that paves the way for radical new forms of treatment.

The researchers measured levels of the antibacterial peptide LL-37 in the urine of healthy children and children with a urinary tract infection. They found that the levels were very low in the former group but high in the latter. Using cultivated human kidney and urinary bladder cells they were then able to identify which cells in the body produce LL-37.

"We were able to show that LL-37 is produced in the epithelial cells of the urinary tracts and the kidneys, and that its build-up and secretion occur within a few minutes after a bacterial attack," says Professor Brauner.

Experiments on mice showed that animals lacking the gene for an antimicrobial peptide almost identical to the human peptide LL-37 are more vulnerable to urinary tract infection. In such animals, the infection was often more serious and the kidneys more swollen and full of bacteria.

"Urinary tract infection is not only painful for the patient, but also an economical burden to the individual and society," says Professor Brauner. "Our findings point to a new way to prevent the development of urinary tract infection by boosting the antibacterial peptide LL-37. For patients suffering from recurrent urinary tract infection, attack would quite simply be the best form of defence."