“Survival of the Fitness” May Mean Multiple Reservoirs for Urinary Tract Infection-causing Bacteria
A new study suggests that the source of recurrent urinary tract infection (UTI) in women is more complex than previously thought, with potential implications for therapy. UTIs are common and occur more frequently in women, many of whom suffer repeated bouts of infection. UTIs are treatable with antibiotics, but the emergence of antibiotic-resistant microbes, combined with the personal and medical costs of care, makes finding better therapeutic strategies a priority. The primary culprit in UTIs is a bacterium called Escherichia coli (E. coli) that is found in the human gut. Most E. coli strains that live in the gut are harmless and actually play a number of beneficial roles, such as helping to prevent harmful bacteria from infecting the gut. Some E. coli, however, acquire the ability, through genetic changes, to infect the bladder, and these uropathogenic E. coli (UPEC) will cause a UTI if accidentally introduced to the urinary tract. Scientists have wondered whether genetic changes that enable E. coli to adapt to a new environment—in this case, the bladder—require a “trade-off” in which the bacteria are less it to flourish in the gut. Answering this question could help in understanding UTIs and identifying the sites of bacterial reservoirs that could contribute to recurrent infection.
To test this idea, scientists studied 45 E. coli strains recovered from urine and fecal samples that were obtained from four women at each of three episodes of UTI. They sequenced the DNA and compared the genes, whole genome sequences, and growth and fitness profiles of the bacteria. Using this approach, the researchers uncovered two different sets of results. In two of the women, the dominant E. coli strains present in the bladder and gut appeared to be genetically the same and did not change across the three UTI episodes. In the other two women, the dominant bacterial strains in the bladder and gut were also the same or very similar within each UTI episode, but changed between the first and third UTI episode. When the researchers compared the genetic profiles of strains from one woman whose bacteria changed between the first and third UTI, the results suggested that E. coli from the third episode would be better at infecting the bladder than E. coli from the first episode—and, thus, might be comparatively weaker in their ability to colonize the gut. However, when the scientists experimentally introduced the two strains into the bladder and gut of mice, they found that E. coli from the third episode grew more robustly than E. coli from the first episode not only in the mouse bladder, but also in the mouse gut—suggesting that greater infectivity in the bladder did not require a fitness trade off for growth in the gut. Previous research in rodent models has shown that some UPEC have the ability to “hide out” within bladder cells only to reemerge later—a possible source of recurrent infection. While this study focused on samples from a small number of women, the findings suggest that E. coli well-suited to cause UTIs may exist and flourish simultaneously in both the gut and the bladder, an aspect of UPEC that can be explored further as researchers consider how to design effective preventive and therapeutic strategies to combat recurrent UTIs.