Molecular Epidemiology and Genome Dynamics of New Delhi Metallo-β-Lactamase-Producing Extraintestinal Pathogenic Escherichia coli Strains from India.
The global dissemination and increasing incidence of carbapenem-resistant, Gram-negative organisms have resulted in acute public health concerns. Here, we present a retrospective multicenter study on molecular characterization of metallo-β-lactamase (MBL)-producing clinical Escherichia 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 of the NDM-1 (69%) type, followed 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 to various extents. 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 isolates revealed higher resistance but a moderate virulence gene repertoire. A subset of NDM-1-positive E. coli isolates was identified as dominant sequence type 101 (ST101) while two strains belonging to ST167 and ST405 harbored NDM-5. A majority of MBL-producing E. coli strains revealed unique genotypes, suggesting that they were clonally unrelated. Overall, the coexistence 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 isolates warrants stringent surveillance and control measures.
Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad, India.
Amit
A
Ranjan
Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad, India.
Sabiha
S
Shaik
Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad, India.
Agnismita
A
Mondal
Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad, India.
Nishant
N
Nandanwar
Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad, India.
Arif
A
Hussain
Robert Koch Institute, Berlin, Germany.
Torsten
T
Semmler
Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad, India.
Narender
N
Kumar
Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad, India.
Sumeet K
SK
Tiwari
Department of Microbiology, D. Y. Patil University, Pimpri, Pune, India.
Savita
S
Jadhav
Robert Koch Institute, Berlin, Germany.
Lothar H
LH
Wieler
Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Gachibowli, Hyderabad, India ahmed.nizi@gmail.com.
Niyaz
N
Ahmed
D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004927:Escherichia coli Infections / Q000382:microbiology; D000072282:Extraintestinal Pathogenic Escherichia coli / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D007194:India; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D010957:Plasmids / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
D001618:beta-Lactamases; C552864:beta-lactamase NDM-1