The successful Escherichia coli O15:K52:H1 clonal group provides a case study for the emergence of multiresistant clonal groups of Enterobacteriaceae generally. Accordingly, we tested the hypotheses that, over time, the O15:K52:H1 clonal group has become increasingly (i) virulent and (ii) resistant to antibiotics. One hundred archived international E. coli O15:K52:[H1] clinical isolates from 100 unique patients (1975 to 2006) were characterized for diverse phenotypic and molecular traits. All 100 isolates derived from phylogenetic group D and, presumptively, sequence type ST393. They uniformly carried the F16 papA allele and papG allele II (P fimbria structural subunit and adhesin variants), iha (adhesin-siderophore), fimH (type 1 fimbriae), fyuA (yersiniabactin receptor), iutA (aerobactin receptor), and kpsM II (group 2 capsule); 85% to 89% of them contained a complete copy of the pap operon and ompT (outer membrane protease). Slight additional virulence profile variation was evident, particularly within a minor diarrhea-associated subset (biotype C). However, in contrast to the clonal group's fairly stable virulence profiles over the past 30؉ years, during the same interval the clonal group members' antimicrobial resistance profiles increased by a mean of 2.8 units per decade (P < 0.001). Moreover, the numbers of virulence genes and resistance markers were positively associated (P ؍ 0.046), providing evidence against antimicrobial resistance and virulence being mutually exclusive in these strains. Thus, the O15:K52:H1 clonal group has become increasingly resistant to antimicrobials while maintaining (or expanding) its virulence potential, a particularly concerning trend if other emerging multiresistant enterobacterial clonal groups follow a similar pattern.Escherichia coli strains of serotype O15:K52:H1 first came to clinicians' attention as significant pathogens in 1986 and 1987, during a year-long, community-wide outbreak of multiresistant infections in South London (23). The outbreak strain exhibited a 100-MDa plasmid and the signature resistance profile ACSSuTTp (resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides, tetracycline, and trimethoprim). Most patients had urinary tract infections, but some had septicemia associated with pneumonia, meningitis, or endocarditis, and three died. E. coli O15:K52:H1 was later documented as a significant extraintestinal pathogen elsewhere in Europe (19,24) and also shown to be distributed widely outside Europe, where it exhibited previously unrecognized phenotypic and genotypic diversity (8). Subsequently, rapid and specific detection of the O15:K52:H1 clonal group by single-nucleotide polymorphism (SNP)-specific PCR was described (12). In a recent Italian study, the O15:K52:H1 clonal group accounted for 16 (11%) of 148 ciprofloxacin-resistant E. coli isolates from uncomplicated urinary tract infections in eight European countries (2003 to 2006), providing evidence of continued clinical importance and a seemingly new resistance phenotype for this clon...