PT  - JOURNAL ARTICLE
AU  - Schreiber, Henry L.
AU  - Conover, Matt S.
AU  - Chou, Wen-Chi
AU  - Hibbing, Michael E.
AU  - Manson, Abigail L.
AU  - Dodson, Karen W.
AU  - Hannan, Thomas J.
AU  - Roberts, Pacita L.
AU  - Stapleton, Ann E.
AU  - Hooton, Thomas M.
AU  - Livny, Jonathan
AU  - Earl, Ashlee M.
AU  - Hultgren, Scott J.
TI  - Bacterial virulence phenotypes of <em>Escherichia coli</em> and host susceptibility determine risk for urinary tract infections
AID  - 10.1126/scitranslmed.aaf1283
DP  - 2017 Mar 22
TA  - Science Translational Medicine
PG  - eaaf1283
VI  - 9
IP  - 382
4099  - http://stm.sciencemag.org/content/9/382/eaaf1283.short
4100  - http://stm.sciencemag.org/content/9/382/eaaf1283.full
AB  - Urinary tract infections (UTIs) are most commonly caused by uropathogenic Escherichia coli (UPEC). In a new study, Schreiber et al. undertook an interdisciplinary analysis of an extensive panel of UTI-associated E. coli strains. They discovered strain-dependent variation in the colonization of two mouse models of UTI. The expression of conserved bacterial behaviors, such as metabolism and motility, diverged markedly among these strains and was a better predictor of bladder colonization than carriage of any set of genes, including previously identified putative urovirulence factors. These findings suggest that UTI risk is determined by the pairing of variable host susceptibilities with bacterial virulence phenotypes governed by both gene content and expression.Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in their urovirulence, that is, their ability to infect the bladder in a mouse model of cystitis. We found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the E. coli strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and metabolism, could be used to predict subsequent colonization of the mouse bladder. Together, our findings suggest that UTI risk and outcome may be determined by complex interactions between host susceptibility and the urovirulence potential of diverse bacterial strains.