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Possible New Advancement To Treat Urinary Tract Infection

The dynamic events that take place during urinary tract infections (UTI) have been identified and a strategy has been developed to combat this most common type. Researchers from the Faculty of Medicine of Baylor and the Faculty of Medicine of Washington discovered that the ITU sequence of events maintains a delicate balance of responses that aim to eliminate bacteria and minimize damage to tissues.

This balance is maintained by the NRF2 pathway, which regulates both tissue damage and the shedding bacteria. The treatment of an animal model for urinary tract infection using the anti-inflammatory drug dimethyl fumarate, ( DMF), reduced tissue damage as well as the bacterial load. This opens up the possibility of DMF being used in the future to manage this condition. Cell Reports published the study.

“We used an animal model to study the effects of DMF treatment on urinary tract infections. We found that NRF2 activation dampened the immune response, reduced the damage that bacteria causes to urothelial cell cells, and promoted activation of RAB27B which kills bacteria in the bladder.

Dr. IndiraMysorekar, who is a Baylor professor of Medicine and a specialist in infectious diseases, said that urinal tract infections are common.

“Uropathogenic E.coli (UPEC) is responsible for more than 85% of all urinary tract infections,” says Dr. Chetanchandra Joshi, a postdoctoral associate at the Mysorekar laboratory. UPECs can attach to urothelial cell walls and reproduce. The current study demonstrated how urothelial cells protect bladder function by fighting UPEC invasion and proliferation.

A dynamic balance in responses

Mysorekar and Joshi discovered that UPEC invasion of urothelial cell urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial urothelial a specific sequence The first was that urothelial cells produced reactive oxygen species (ROS) within the first hour after infection. These ROS are highly active compounds that kill bacteria. ROS can damage the bladder if it is not stopped.

Joshi adds, “We found that ROS accumulation activated an anti ROS response in urothelial cell, the NRF2 pathway. This minimized the damage that excess ROS can cause to urothelial cell, ” Joshi says.

NRF2 is found in cells’ cytoplasm attached to KEAP1 protein. When ROS levels reach a certain point, NRF2 is released from KEAP1 to enter the nucleus of cells, activating a number of genes. Joshi says that some of these genes make proteins that block ROS, while others limit inflammation.

Joshi emphasizes that “Interestingly, Rab27b is one of the genes activating NRF2, which promotes the removal of UPEC urothelial cell “. These coordinated events mediate UPEC removal while preserving integrity of bacteria-infected cells.

A possible new way to fight UPEC

A new strategy for fighting UPEC infection was discovered by understanding the process. Joshi says that activating NRF2 is involved in both the neutralization ROS which protects urothelial cells and the removal of UPEC. These results suggested that a drug activating NRF2, like DMF, could be used to clear UPEC infections.

DMF has been approved by the US FDA for the treatment of multiple sclerosis and inflammatory conditions. It also reduces inflammation. The Spanish Agency for Medicines and Health Products also approves DMF.

Mysorekar adds, “We used an animal model to demonstrate that DMF treatment activated the NRF2, reduced the level of bacteria damage to urothelial cell, and promoted activation of RAB27B which killed the bladder bacteria. These findings suggest that this approach could be explored further as a possible treatment for UTIs.

Recurrent urinary tract infections are more common in women. This can cause chronic inflammation, damage to the bladder’s lining, and even chronic infection. The microbiome, or the good bacteria in the body, is also negatively affected by antibiotic treatment and encourages the growth of antibiotic-resistant bacteria.

Mysorekar said that the most exciting aspect of his research was the discovery of an antibiotic-free treatment that would reduce inflammation and contain infection. While there is still much to be done before the treatment can be implemented in the clinic, DMF therapy has the potential of helping millions of women with this condition.

Amy Mora and Paul A. Felder, who worked previously at the University of Washington School of Medicine, are also contributors to this project.

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