Research ArticleGenomics

Genomic Diversity and Fitness of E. coli Strains Recovered from the Intestinal and Urinary Tracts of Women with Recurrent Urinary Tract Infection

Science Translational Medicine  08 May 2013:
Vol. 5, Issue 184, pp. 184ra60
DOI: 10.1126/scitranslmed.3005497

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UTI Bugs Without Barriers

Urinary tract infections (UTIs) are among the most common infections in women, with uropathogenic Escherichia coli (UPEC) being the major cause. Recurrent infections are troublesome and can persist for years. Studies in mice have led to the realization that UPEC strains can specialize so that once they enter the urinary tract they can invade bladder tissue, forming protected bacterial communities that contribute to recurrent UTIs. A prevailing view is that recurrent UTIs also represent repeated movement of UPEC strains from the gut to the bladder. This migration is thought to be unidirectional, reflecting a view that fitness (ability to succeed) in the bladder comes at a cost of loss of fitness in the gut. We reexamined this fitness “trade-off” by characterizing the genomes of urine and fecal E. coli isolates obtained from four healthy women, enrolled in a large patient study of recurrent UTI, who each had three recurrent UTIs. In two women, the dominant UPEC strain in both their urine and feces was the same throughout all three UTIs. In the other two, the UPEC strain present in both urine and feces in the initial UTI episode was replaced by a different strain at the third recurrence. In mouse models of bladder infection and gut colonization, the strain that dominated in the later UTI episode had increased fitness in both habitats compared to the strain it replaced. Increased fitness correlated with genetic differences affecting nutrient utilization and virulence. Thus, recurrent UTI is complex and may involve strains moving freely, without fitness trade-offs, between the bladder and the gut in addition to invasion of bladder tissue. Whereas further human studies are needed to assess the role of gut bacteria and their genetic characteristics during recurrent UTI, this broader view could lead to new approaches for prevention, diagnosis, and treatment of this troublesome infection.