Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infections (UTIs). The increase in the human use of fluoroquinolones as a first-line agent for uncomplicated UTIs has contributed to the emergence and spread of multidrug-resistant strains. Indeed, our group has studied the genomic epidemiology and virulence of sequence type (ST)131, the most globally dominant fluoroquinolone-resistant UPEC clone and a major cause of UTI and bloodstream infections associated with limited treatment options. Recent surveillance has identified ST1193 as the second most dominant fluoroquinolone-resistant UPEC clone (after ST131). The global emergence of ST1193 follows a similar timeline to ST131, and sequence analysis has revealed the ST1193 linage consists of two major clades. These two clades are distinguished by recombination of a 30.4 kb region encompassing the capsular biosynthesis locus, causing a switch from K5 (clade 2) to K1 (clade 1). To study the involvement of the capsule in the virulence of the ST1193 linage, two K1 and two K5 capsule representative strains were studied. Mutation of the kpsD gene, which encodes an outer membrane protein essential for surface expression of the capsule polysaccharide, abolished capsule production in all strains as demonstrated using lytic K1 and K5 specific phage. Survival of the kpsD mutants in whole blood was also examined using single and mixed competitive assays. While the wild-type strains were able to survive in whole blood, survival of the kpsD mutants was highly attenuated. We have now tagged the K1 and K5 wild-type strains using different antibiotic resistance gene markers, and are examining the differential contribution of the polysialic acid-containing K1 capsule compared to the glycosaminoglycan-containing K5 capsule in ST1193 virulence.