Evaluating and targeting C5a receptor in pyelonephritis

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Urinary tract infection (UTI) caused by the microbe E. coli is a common infectious disease. It is especially frequent in women and children and is a particular problem for patients with diabetes and renal transplants. Although antibiotics can be used to treat the disease, frequent recurrence or persistence of infection is still a big problem. A better understanding of how bacteria are able to invade, survive and grow in the urinary tract, and the mean(s) by which they cause tissue damage is required for improving current treatment. The inflammatory mediators generated in our body in response to infection play essential roles in the first line of host defense against pathogens; however, they can also cause harm when present in excess or are dysregulated. C5a is a potent inflammatory mediator which has been shown to be associated with various inflammatory and infectious diseases. The proposed research is to work out if and how C5a could participate in the development of kidney and bladder infection and contribute to the recurrence or persistence of infection. If we are successful in showing how C5a acts on different cell types within the urinary tract tissues to promote bacteria invasion, survival and growth, this may offer a valuable means to block the action of C5a and thus prevent and treat UTI.