The complete genome sequence of uropathogenic Escherichia coli strain CFT073 has been determined, revealing a complex mosaic structure. A comparison of CFT073, enterohemorrhagic E. coli EDL933, and the nonpathogenic strain MG1655 shows that only 39.2% of their combined proteins are common to all three. The pathogen genomes differ significantly from each other and from the benign strain. CFT073 lacks genes for type III secretion system and phage- and plasmid-encoded toxins found in some diarrheagenic E. coli. It is rich in genes for fimbrial adhesins, autotransporters, iron-sequestration systems, and phase-switch recombinases. The large pathogenicity islands of CFT073 differ from those of other uropathogenic strains, J96 and 536. Comparisons indicate that extraintestinal pathogenic E. coli arose independently from multiple clonal lineages. Despite this, different E. coli pathotypes maintain a remarkable synteny of common, vertically evolved genes, while many islands have been acquired by horizontal transfer events in each strain. E. coli is a diverse species, with some strains being harmless commensals and others causing significant disease. Extraintestinal E. coli, including uropathogens, are life-threatening pathogens. The uropathogenic group is responsible for 70–90% of acute cystitis cases and 250,000 pyelonephritis cases annually in the US. The CFT073 genome is 5,231,428 bp long, with five cryptic prophage genomes. It is 590,209 bp longer than MG1655 and similar in size to EDL933. The CFT073 genome contains 2,004 genes, of which 204 are also present in EDL933. Many of these genes have unknown functions or are associated with phage or insertion sequence elements. The CFT073-specific islands total 1.303 Mb, while the MG1655-specific sequences amount to 715.7 kb. The genome analysis reveals that the CFT073-specific islands contain genes for potential virulence factors, including adhesins, iron-uptake systems, and transport systems. The differences in disease potential between enterohemorrhagic and uropathogenic E. coli are reflected in the absence of certain genes in CFT073. The CFT073 genome has a unique set of genes for fimbrial adhesins, secreted autotransporters, and phase-switch recombinases. The genome also contains genes for type IV pili, which are involvedThe complete genome sequence of uropathogenic Escherichia coli strain CFT073 has been determined, revealing a complex mosaic structure. A comparison of CFT073, enterohemorrhagic E. coli EDL933, and the nonpathogenic strain MG1655 shows that only 39.2% of their combined proteins are common to all three. The pathogen genomes differ significantly from each other and from the benign strain. CFT073 lacks genes for type III secretion system and phage- and plasmid-encoded toxins found in some diarrheagenic E. coli. It is rich in genes for fimbrial adhesins, autotransporters, iron-sequestration systems, and phase-switch recombinases. The large pathogenicity islands of CFT073 differ from those of other uropathogenic strains, J96 and 536. Comparisons indicate that extraintestinal pathogenic E. coli arose independently from multiple clonal lineages. Despite this, different E. coli pathotypes maintain a remarkable synteny of common, vertically evolved genes, while many islands have been acquired by horizontal transfer events in each strain. E. coli is a diverse species, with some strains being harmless commensals and others causing significant disease. Extraintestinal E. coli, including uropathogens, are life-threatening pathogens. The uropathogenic group is responsible for 70–90% of acute cystitis cases and 250,000 pyelonephritis cases annually in the US. The CFT073 genome is 5,231,428 bp long, with five cryptic prophage genomes. It is 590,209 bp longer than MG1655 and similar in size to EDL933. The CFT073 genome contains 2,004 genes, of which 204 are also present in EDL933. Many of these genes have unknown functions or are associated with phage or insertion sequence elements. The CFT073-specific islands total 1.303 Mb, while the MG1655-specific sequences amount to 715.7 kb. The genome analysis reveals that the CFT073-specific islands contain genes for potential virulence factors, including adhesins, iron-uptake systems, and transport systems. The differences in disease potential between enterohemorrhagic and uropathogenic E. coli are reflected in the absence of certain genes in CFT073. The CFT073 genome has a unique set of genes for fimbrial adhesins, secreted autotransporters, and phase-switch recombinases. The genome also contains genes for type IV pili, which are involved