Tracking the emergence and dissemination of a bla _NDM-23 Gene in a Multi-Drug Resistance Plasmid of Klebsiella pneumoniae

Abstract

Objectives

Since the discovery of bla _NDM-1, NDM beta-lactamases have become one of the most widespread carbapenemases worldwide. To date, 28 different NDM variants have been reported but some, such as bla _NDM-23, have not been characterized in detail yet. Here, we describe the emergence of a novel bla _NDM-23 allele from a bla _NDM-1 ancestor and the multidrug resistant plasmid that has disseminated it through a K. pneumoniae ST407 clone in several Spanish hospitals.

Methods

Between 2016 and 2019, 1,972 isolates were collected in an epidemiological survey for ESBL-producing Klebsiella pneumoniae in the Comunitat Valenciana (Spain). Three carbapenem resistant strains failed to be detected by CPE screening tests. These isolates carried a bla _NDM-23 gene. To characterize this gene, its emergence, and dissemination, we performed antimicrobial susceptibility tests, hybrid sequencing with Illumina and Nanopore technologies, and phylogenetic analyses.

Results

The MICs of the bla _NDM-23 variant were identical to those of the bla _NDM-1. The bla _NDM-23 variant was found in 14 isolates in a 97 Kb non-mobilizable, multidrug-resistant plasmid carrying 19 resistance genes for 9 different antimicrobial families. In this plasmid, the bla _NDM-23 gene is located in the variable region of a complex class-1 integron with a singular genetic environment. The short genetic distance between bla _NDM-23-producing isolates reflects a 5-year-long clonal dispersion involving several hospitals and interregional spread.

Conclusions

We have characterized the genomic and epidemiological contexts in the emergence and community spread of a new bla _NDM-23 allele in an MDR-plasmid of Klebsiella pneumoniae.

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Genomic, epidemiologic and phylogenetic analyses of the emergence of a new NDM allele provide information on the rapid changes underlying the spread of antimicrobial resistance genes and strains in Klebsiella pneumoniae.

Importance

At a time when antimicrobial resistance has become one of the biggest concerns worldwide, the emergence of novel alleles and extremely drug-resistant plasmids are a threat to public health worldwide. More so when they produce carbapenem resistance in one of the most problematic pathogens in clinical settings, such as Klebsiella pneumoniae. Here, we have used genomic epidemiology to describe the emergence of a novel NDM-23 allele and identify it in a MDR plasmid that has been disseminated through a K. pneumoniae ST407 clone in several hospitals in a Spanish region. By means of bioinformatic and phylogenetic analyses, we have been able to trace the evolutionary and epidemiological route of the new allele, the hosting plasmid, and the strain that carried both of them from Pakistan to Spain. A better understanding of the NDM-producing K. pneumoniae populations and its plasmids has made evident the spread of this clone through the region, enhancing the importance of genomic surveillance in the control of antimicrobial resistance.