Study uncovers potential mechanism behind chronic UTIs

New research published in Science Advances suggests that urinary tract infections (UTIs) may persist following treatment due to the capability of numerous bacteria strains to invade and hide in the bladder wall.¹

"Based on our results, next-generation diagnostics for UTIs could focus on identifying ‘bad’ bugs based on how the body responds, rather than trying to spot the presence of problem bacteria among the background noise of the microbiome," says Carlos Flores, PhD.

For the study, investigators at the University College London (UCL) developed a 3D urine-tolerant human urothelial to mimic the biological environment and function of human urothelial tissue. Specifically, they assessed responses of the artificial bladders to exposure of 6 bacterial species: Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus agalactiae, and Klebsiella pneumoniae.

Findings showed that several uropathogens were able to invade intracellularly without forming intracellular bacteria communities (IBCs). Commensal Escherichia coli was also found to invade frequently and form large IBCs, which the authors say indicates that invasion is a “shared survival strategy, not solely a virulence hallmark.”¹

Further, they noted that uropathogenic Escherichia coli FimH was important in IBC formation, but not essential for invasion.

Jennifer Rohn, PhD, a professor at the UCL division of medicine and senior author of the study, explained their findings in a news release, “Some species of both ‘good’ and ‘bad’ bugs formed pods within the bladder wall, most likely as a way of surviving in this harsh environment. If this happens with a friendly bug, this isn’t a problem. But if the bug is causing an infection, this poses a serious problem for diagnosis and treatment because the bacteria aren’t necessarily going to be detected in a urine sample or be in a position where oral antibiotics can reach them.”²

The investigators also found that production of cytokines and the shedding of the top layer of the bladder wall were triggered by more aggressive bacteria strains, indicating that the cells can distinguish highly cytotoxic strains.

“Based on our results, next-generation diagnostics for UTIs could focus on identifying ‘bad’ bugs based on how the body responds, rather than trying to spot the presence of problem bacteria among the background noise of the microbiome. There are so many species and strains of bacteria in the human bladder that we don’t fully understand, but the body seems to be pretty good at telling friend from foe,” said lead author Carlos Flores, PhD, in the news release.² Flores is a Human Frontier Science Program fellow at the University of Basel in Switzerland.

The authors indicated that further work based on these findings is warranted.

“This study confirms what many women who’ve struggled with persistent UTIs already know, which is that the current methods of diagnosing and treating these infections are inadequate. Urine dipstick tests are too likely to miss infections hiding in the bladder wall, especially when a patient’s first response to discomfort is to drinks lots of water, which dilutes the test. Not all bugs can be cultured in the lab, and even if they could be that doesn’t tell us if this strain is the cause of an infection or if its position in the bladder wall would make the standard 3-day course of antibiotics unlikely to eradicate it,” Rohn concluded.²

References

1. Flores C, Ling J, Loh A, et al. A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and commensals. Sci Adv. Published online November 8, 2023. Accessed November 9, 2023. doi:10.1126/sciadv.adi9834

2. Artificial bladders used to shine light on bugs that cause urinary tract infections. News release. University College London. November 6, 2023. Accessed November 9, 2023. https://www.newswise.com/articles/artificial-bladders-used-to-shine-light-on-bugs-that-cause-urinary-tract-infections?sc=mwhr&xy=10016681