Seeking a Genetic Signature for Urinary Tract Infections
In a recent study, scientists sought to determine whether there is a universal “genetic signature(s)” defining the ability of UPEC to cause disease. Potential candidates for such a signature include so-called putative urovirulence factor (PUF) genes that have been found to be enriched in UTI-associated E. coli versus “regular” E. coli. To pursue this question, the researchers studied 21 representative E. coli strains obtained from the urine of 14 women who suffered from recurrent UTIs. They compared and “scored” these strains based upon how many PUF genes each one possessed. By comparing this score with how well each strain infected bladders in a standard female mouse model, the researchers determined that having a higher PUF gene score did not correlate with either strength (robust, variable, or deficient) of an acute infection, or with the ability to cause chronic infection in one mouse model. However, the investigators found that mice that differed genetically reacted differently to infection—for example, two bacterial strains that caused robust bladder infection in one mouse model were much less effective in a second mouse model. Rather than ignore the differences between the mouse models, the scientists investigated whether that could provide a clue to differences in infectivity. Using the first mouse model, they found that variation in the activity of certain genes regulating core E. coli functions correlated with how effectively the strains infected the animals. Bacterial strains that more robustly infected the mice correlated with markers of greater UTI severity in women, such as higher white blood cell counts in urine. Together, the study findings suggest that rather than a signature set of genes consistently determining virulence, a more complex and dynamic interplay between E. coli strains and their host environment determines infection and subsequent disease.