Clarity on Epigenetic Mechanisms Behind Chronic UTI

A study in mice published in Nature Microbiology discovers that the microbiological substrate for chronic UTI can contain localized epigenetic modifications that increase the likelihood of further infections. Previous urinary tract infections (UTIs) are recognized to predispose individuals to subsequent infections, but the processes underlying recurrences are unknown. Researchers from Washington University School of Medicine in St Louis expanded on prior findings that demonstrated distinct epithelial cellular alterations after UTIs in mouse bladders, resulting in varied outcomes. The current study, “Uropathogenic Escherichia coli infection-induced epithelial trained immunity impacts urinary tract disease outcome,” compared urothelial stem cell (USC) lines isolated from mice with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, and found epigenetic changes, including differences in chromatin accessibility, DNA methylation, and histone modification. A News & Views article on the research was published in the same journal issue.

The previous infection causes urothelial stem cell alterations that persist over several generations of cell culture, indicating a probable epigenetic mutation within those cells, according to one clue the researchers followed. Epigenetic alterations are changes in how DNA is accessed and, as a result, in which genes are expressed rather than changes in the DNA sequences of the cells. These kinds of modifications can have an impact on normal cell function and, in this case, immune responses.

They discovered that UPEC infection functions as an epi-mutagen, changing the functional activity of urothelial cells, resulting in remodeling and a changed or trained innate response to future infections. The findings show that a mucosal bacterial infection causes particular epigenetic alterations in mucosal epithelial stem cells.

While the research on mice does not propose a remedy, it does highlight previously undiscovered pathways that can help future research in designing remedies for chronic UTIs. This could be a substantial and actionable advancement in our understanding of the problem, which now only offers tips on how to wipe after using the toilet, ideas to keep genitals dry, and urging large quantities of cranberry juice consumption as techniques to prevent reinfection.

Even if there is no current cure, the study may be welcome news for those suffering from chronic UTI because it confirms that the problem is an epigenomic-based immunity issue rather than a failure on their part to follow basic hygiene instructions or consume enough cranberry juice.

Source Link