By controlling both the possible harm to organs and the removal of micro-organisms, the NRF2 system stands forth as a crucial contribution to this equilibrium.
The FDA-approved anti-inflammatory medicine dimethyl fumarate (DMF), a known recognized NRF2 activator, decreased tissue injury or bacterium load in an animal study of UTI, suggesting that DMF can one day be utilized to cure this ailment. The research was published in the journal Cell Reports.
A New Technique To Fight Urinary Tract Infections Is Discovered
As per an estimate, millions of people, including males and females, suffer from this disease. However, this has been more seen in females, and this new technique can help them get rid of the same easily now.
More development is yet expected with this novel option of UTI counter by experts.
The discovery of the dynamic processes that occur throughout urinary tract infections (UTI) has offered a novel possible technique to battle this illness, which is the largest frequent form.
Scientists observed that throughout a UTI, the chain of actions maintains a careful ratio among reactions aimed at eradicating the bacterium & those aimed at minimizing any tissue injury that could ensue.
“Urinary tract infections are not only common but typically recurrent and tend to give rise to antibiotic-resistant bacteria, a serious medical concern,” said corresponding author Dr. Indira Mysorekar, E. L. Wagner Endowed Professor.
“More than 85% of UTI are caused by uropathogenic E. coli (UPEC), bacteria that can attach to the surface of the epithelial cells lining the inside of the bladder, called urothelial cells,” said first author Dr. Chetanchandra S. Joshi, a postdoctoral associate in the Mysorekar lab. “Attached UPEC can then enter the urothelial cells, where they reproduce. In the current study, we looked at how urothelial cells fight back UPEC invasion and proliferation while preserving their integrity, which is essential for proper bladder function.”
Studying with lab-grown urothelial cells, Mysorekar, Joshi, and their collaborators observed that UPEC infiltration of urothelial cells was accompanied by a specific series of activities.
Urothelial cells first fought themselves by creating reactive oxygen species (ROS), extremely reactive chemicals that destroy bacterium, in the first hrs following the invasion. Nevertheless, if ROS levels are high enough, they can harm urothelial cells. This is bad for the urethra.
“We found that accumulation of ROS activated an anti-ROS response in urothelial cells, called the NRF2 pathway, that minimized the damage excess ROS could cause to the urothelial cells,” Joshi said.
The NRF2 molecule is found in the cells’ cytoplasm, linked to another enzyme known as KEAP1. “When ROS levels reach a particular threshold, NRF2 separates from KEAP1 and enters the cell nucleus, where it activates several genes. Some of these genes create anti-oxidant proteins, while others make anti-inflammatory proteins, “Joshi remarked.
“Interestingly, one of the genes NRF2 activates is Rab27b, which promotes the elimination of UPEC from urothelial cells,” Joshi said. “Together, these coordinated events mediate the elimination of UPEC while preserving the integrity of the cells attacked by the bacteria.”
DMF has been authorized by the FDA to treat inflammation disorders, including multiple sclerosis, by reducing inflammatory reactions.
Repeated UTI is more common in females, and it could result in persistent irritation, mucosa damage, and infections. Antibiotic therapy has a deleterious impact on the microbiota, the cell’s “good bacteria,” and encourages the growth of antibiotic-resistant pathogens.
“The most exciting part about this work was identifying a non-antibiotic-based therapy that contained the infection and reduced inflammation,” said Mysorekar, who also is a professor of molecular virology and microbiology at Baylor. “Although much work is needed before it reaches the clinic, treatment with DMF has the potential of helping millions of women affected by this condition.”
