One size doesn’t fit all: unraveling the diversity of factors and interactions that drive E. coli urovirulence

Urinary tract infections (UTIs) are common (with 11 million cases annually in the USA), costly (with $5 billion spent per year), and increasingly antibiotic resistant (1). The clinical manifestations and symptomatologies of UTIs are strikingly complex and result from the interactions between diverse uropathogens and host urothelial tissues. The most common cause of UTIs is UPEC, which cause up to 80% of community-acquired UTIs and 65% of hospital-acquired UTIs (1). Despite appropriate treatment for the initial infection, UTIs are frequently recurrent as 25–35% of initial infections are followed by a recurrent UTI (rUTI) (2). In addition, the high level of same-strain recurrences, in which a single bacterial strain (as defined by genetic identity) causes two or more consecutive UTIs, strongly suggests that there exist non-pathogenic reservoirs within hosts (2). One established reservoir is the gastrointestinal tract (GIT) microbiota (3). UPEC strains can maintain non-pathogenic colonization of the GIT, where they form a reservoir and subsequently seed extraintestinal infections such as UTI. In this review, we detail critical gaps in our understanding of the pathogenic and non-pathogenic colonization of UPEC in different habitats in the host and describe a new perspective on UTI susceptibility that better reflects the complexity of this disease.