Potential new strategies to combat urinary tract infection (UTI)

Recognizing the dynamic events that occur during urinary tract infection (UTI) reveals a new potential strategy to combat this disease, which is considered the most common type of infection

The NRF2 pathway has become a key contributor to this balance by regulating the potential damage to tissues and the elimination of bacteria

Corresponding author Dr.

"More than 85% of urinary tract infections are caused by urinary tract pathogenic Escherichia coli (UPEC), which can attach to the surface of epithelial cells on the inner wall of the bladder, called urothelial cells," first author Chetanchandra S.

Dynamic equilibrium of reaction

Mysorekar, Joshi and their colleagues used urothelial cells cultured in the laboratory and found that after UPEC invaded urothelial cells, there was a precise sequence of events

Joshi said: "We found that the accumulation of ROS activates the anti-ROS response in urothelial cells, called the NRF2 pathway, which minimizes the damage that excess ROS may cause to urothelial cells

The NRF2 protein is located in the cytoplasm of the cell and binds to another protein called KEAP1

"Interestingly, one of the genes activated by NRF2 is Rab27b, which promotes the elimination of UPEC in urothelial cells," Joshi said

A potential new method against UPEC

Understanding the process after UPEC infection reveals a potential new strategy to combat this disease

DMF is approved by the FDA to treat inflammation, such as multiple sclerosis, by inhibiting inflammation

Mysorekar said: "Through the animal model of UTI, we proved that DMF can activate NRF2, suppress the immune response, limit the damage caused by bacteria to urothelial cells, and promote the activation of RAB27B, thereby removing bacteria from the bladder

Women often have recurrent urinary tract infections, which can lead to chronic inflammation, extensive bladder mucosal damage and chronic infections

"The most exciting part of this work is the identification of a non-antibiotic therapy that includes infection and reduces inflammation," said Mysorekar, who is also a professor of molecular virology and microbiology at Baylor University

“NRF2 promotes urothelial cell response to bacterial infection by regulating reactive oxygen species and RAB27B expression” 19 October 2021, Cell Reports .