Urinary Tract Infections (UTIs)
UTIs are common in humans, resulting in an estimated 8 million outpatient visits and over $2 billion in health care costs in the United States each year. UTI is also one of the most common uses of antibiotics and likely a substantial contributor to the emergence of bacterial antibiotic resistance. The dominant etiologic agent of UTI in humans is uropathogenic Escherichia coli (UPEC), which accounts for up to 85% of community acquired UTIs. Investigators at the Center for Women’s Infectious Disease Research have a long history of mechanistic studies of E. coli UTI pathogenic cascade. E. coli progresses through a series of distinct stages, from association with the bladder to the formation of intracellular biofilm-like communities, and release from this niche into the bladder lumen to allow re-infection of the epithelium. Our understanding of virulence mechanisms has allowed us to demonstrate novel therapeutic strategies. Promising avenues include anti-adhesion molecules targeting E. coli lectin FimH, small molecules capable of preventing biofilm formation, and the acquisition of iron through siderophores.
Uropathogenic E. coli produce adhesive pili fibers on their surface (upper right) which allow them to bind to (upper left and lower right) and invade into (upper and lower left) bladder epithelial cells.
Uropathogenic E. coli: (green) replicate within bladder cells to form large intracellular bacterial communities (IBCs) which are protected from many host defenses and antibiotics.
When IBCs mature bacteria (yellow) detach and flux out of infected host cells, filament and go on to infect new host cells.
Network representation of virulence-associated gene carriage in over 300 clinical E.coli isolates reveals four community types suggesting distinctive strategies for causing urinary tract infections.