Emergence of NDM-5-producing Escherichia coli sequence type 167 clone in Italy

Abstract

The emergence of carbapenemase-producing Enterobacteriaceae (CPE) is a critical concern worldwide. In Italy, CPE isolates are very frequent, with the KPC enzyme types strongly predominant whereas the New Delhi metallo-β-lactamase (NDM) enzymes are extremely rare. Here we report the first detection of NDM-5-producing Escherichia coli sequence type 167 (ST167) isolates from two patients with urinary tract infection (Ec001 and Ec002 from urines), including one with colonisation (Ec003 from faeces) admitted to the same hospital 2 months apart in 2017. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. The carbapenemase type was identified both by phenotypic and genotypic methods. Isolate genotypes were investigated by phylogenetic typing, multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Next-generation sequencing (NGS) was used to obtain complete sequences of plasmids. The three E. coli isolates carried the bla gene, shared the same resistance phenotype and belonged to ST167. By PFGE, isolates showed the same profile, suggesting that they were the same strain. NGS revealed that the bla gene was located on a 99-kb multireplicon plasmid (designed pNDM-5-IT) with a peculiar scaffold constituted by four replicons of the IncF type (FIA, FIB and two copies of the FII replicon). pNDM-5-IT plasmid harboured multiple resistance and virulence determinants, including the arginine deaminase (ADI) cluster never found associated with plasmids before. Since NDM-5-producing E. coli ST167 has been regarded as a successful epidemic clone in China, the emergence of such a clone carrying a plasmid associated both with multiresistance and virulence could be a public-health threat.

Dissemination of the bla NDM-5 Gene via IncX3-Type Plasmid among Enterobacteriaceae in Children

“…According to the complete sequences of the plasmids, the genetic background of bla NDM-5 in pNDM-Z244 was similar to that in the classical plasmid pNDM-MGR194, i.e., IS3000-IS5-⌬ISAba125bla NDM-5 -bla MBL -trpF-dsbC-IS26-umuD. In contrast, the bla NDM-5 gene in pNDM-5-IT was more complex and was found in the dfrA12-aadA2-ISCR1-bla NDM-5 complex integron (9).…”

“…New Delhi metallo-␤-lactamase-5 (NDM-5) was first identified in a multidrugresistant Escherichia coli ST648 isolate in the United Kingdom in 2011 (4). Since then, NDM-5 has been reported all over the world, including in Egypt (5), South Korea (6), China (7), the United States (8), Italy (9), and Spain (10). However, NDM-5 has mainly been identified in E. coli and a few other Enterobacteriaceae isolates (11).…”

The Arginine Deiminase Operon Is Responsible for a Fitness Trade-Off in Extended-Spectrum-β-Lactamase-Producing Strains of Escherichia coli

“…The arc operon also contains genes encoding the ArgR and ArcD proteins, involved in the regulation of the operon and transport of arginine, respectively (21). Other plasmids from E. coli strains have been shown to carry an arc operon: pIP1206 (22), pJIE186-2 (23), pNDM-5-IT, and pCTXM15_EC8 (24).…”

Precision Medicine and Mysteries in Clinical Microbiology: Rationalizing Epidemiology, Genotype, and Phenotype To Guide Therapeutics

“…The IncX3 plasmid found in this isolate did not contain carbapenemase genes but contained the cephalosporinase bla CTX-M-15 . Rather, bla NDM was in an IncF plasmid surrounded by a genetic environment like that of other bla NDM plasmids in E. coli from Asia and Europe (5). Similarly, K. pneumoniae ST16, also isolated in this case, has been reported harboring bla NDM-5 in Asia and Europe.…”