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The global dissemination amidst increasing incidence of carbapenem-resistant, Gram-negative organisms has resulted in acute public health concerns. Here, we present a retrospective multicenter study on molecular characterization of metallo-beta-lactamase (MBL) producing clinical E. coli isolates recovered from extraintestinal infections in two hospitals in Pune, India. We screened a large sample size of 510 E. coli isolates for MBL production wherein we profiled their molecular determinants, antimicrobial resistance phenotypes, functional virulence properties, genomic features and transmission dynamics. Approximately ∼8% of these isolates were MBL producers, the majority of which were NDM-1 (69%) type followed subsequently by NDM-5 (19%), NDM-4 (5.5%) and NDM-7 (5.5%). MBL producers were resistant to all antibiotics tested, except for colistin, fosfomycin and chloramphenicol which were effective up to a varying extent. Plasmids were found to be an effective means of dissemination of NDM genes and other resistance traits. All MBL producers adhered to and invaded bladder epithelial (T24) cells and demonstrated significant serum resistance. Genomic analysis of MBL producing E. coli revealed higher resistance but a moderate virulence gene repertoire. A subset of NDM-1 positive E. coli was identified as dominant sequence type 101 while two strains belonging to ST167 and ST405 harbored NDM-5. A majority of MBL producing E. coli strains revealed unique genotypes suggesting they were clonally unrelated. Overall, the co-existence of virulence and carbapenem resistance in clinical E. coli isolates is of serious concern. Moreover, the emergence of NDM-1 among the globally dominant E. coli ST101 warrants stringent surveillance and control measures.