ABSTRACTIn view of the epidemiological success of CTX-M-15-producing lineages ofEscherichia coliand particularly of sequence type 131 (ST131), it is of significant interest to explore its prevalence in countries such as India and to determine if antibiotic resistance, virulence, metabolic potential, and/or the genetic architecture of the ST131 isolates differ from those of non-ST131 isolates. A collection of 126E. coliisolates comprising 43 ST131E. coli, 40 non-ST131E. coli, and 43 fecalE. coliisolates collected from a tertiary care hospital in India was analyzed. These isolates were subjected to enterobacterial repetitive intergenic consensus (ERIC)-based fingerprinting, O typing, phylogenetic grouping, antibiotic sensitivity testing, and virulence and antimicrobial resistance gene (VAG) detection. Representative isolates from this collection were also analyzed by multilocus sequence typing (MLST), conjugation, metabolic profiling, biofilm production assay, and zebra fish lethality assay. All of the 43 ST131E. coliisolates were exclusively associated with phylogenetic group B2 (100%), while most of the clinical non-ST131 and stool non-ST131E. coliisolates were affiliated with the B2 (38%) and A (58%) phylogenetic groups, respectively. Significantly greater proportions of ST131 isolates (58%) than non-ST131 isolates (clinical and stoolE. coliisolates, 5% each) were technically identified to be extraintestinal pathogenicE. coli(ExPEC). The clinical ST131, clinical non-ST131, and stool non-ST131E. coliisolates exhibited high rates of multidrug resistance (95%, 91%, and 91%, respectively), extended-spectrum-β-lactamase (ESBL) production (86%, 83%, and 91%, respectively), and metallo-β-lactamase (MBL) production (28%, 33%, and 0%, respectively). CTX-M-15 was strongly linked with ESBL production in ST131 isolates (93%), whereas CTX-M-15 plus TEM were present in clinical and stool non-ST131E. coliisolates. Using MLST, we confirmed the presence of two NDM-1-positive ST131E. coliisolates. The aggregate bioscores (metabolite utilization) for ST131, clinical non-ST131, and stool non-ST131E. coliisolates were 53%, 52%, and 49%, respectively. The ST131 isolates were moderate biofilm producers and were more highly virulent in zebra fish than non-ST131 isolates. According to ERIC-based fingerprinting, the ST131 strains were more genetically similar, and this was subsequently followed by the genetic similarity of clinical non-ST131 and stool non-ST131E. colistrains. In conclusion, our data provide novel insights into aspects of the fitness advantage ofE. colilineage ST131 and suggest that a number of factors are likely involved in the worldwide dissemination of and infections due to ST131E. coliisolates.