In the search for new ways to combat urinary tract infections, researchers have shown that an experimental drug that stabilizes a protein called HIF-1alpha protects human bladder cells and mice against a major UTI pathogen.
The drug may eventually provide a therapeutic alternative or complement to standard antibiotic treatment, say study authors from the University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences.
The study was published online in by PLOS Pathogens (April 30, 2015).
HIF-1alpha is known to influence the innate immune response, researchers say. Like many regulator proteins, HIF-1alpha is relatively short-lived. To increase HIF-1alpha levels, researchers have developed drugs that delay its breakdown. This same pathway has been the target for drugs now in advanced clinical trials for treatment of anemia.
In the current study, lead author Victor Nizet, MD, and colleagues explored the use of HIF-1alpha-stabilizing drugs to boost the innate immune response to uropathogenic Escherichia coli (UPEC) bacteria, a major cause of UTIs. In healthy human urinary tract cells, treatment with the drugs increased HIF-1alpha levels. Such cells were then more resistant to UPEC attachment, invasion, and killing than human urinary tract cells with normal HIF-1alpha levels, Dr. Nizet’s team said in a University of California, San Diego news release.
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