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. 2025 Apr 8;28(5):112369.
doi: 10.1016/j.isci.2025.112369. eCollection 2025 May 16.

First characterization of four repeat regions with the bla NDM-1 carried on an IncFII plasmid in Enterobacter hormaechei

Yi Liu  1 , Xiaojing Liu  2   3 , Ruishan Liu  1 , Hao Xu  1 , Mantao Chen  4 , Jiajie Qian  5 , Beiwen Zheng  1   3   6   7
Affiliations

First characterization of four repeat regions with the bla NDM-1 carried on an IncFII plasmid in Enterobacter hormaechei

Yi Liu et al. iScience. .

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a critical threat to global health, and multicopy resistance genes are a potential contributor to increased resistance. This study investigates a novel arrangement of four bla NDM-1 genes in tandem on an IncFII plasmid from Enterobacter hormaechei. Whole-genome sequencing (WGS) of E. hormaechei isolates L710hy identified a four-tandem repeat of the bla NDM-1 gene, with each copy's environment nearly identical (ISCR1-aph(3')-VI-ISAba125-bla NDM-1-ble-iso-tat-dsbD-cutA-sul1-ISCR1). The study suggests a correlation between the bla NDM-1 copy number and minimum inhibitory concentration (MIC) values for carbapenems, though further research is needed to confirm this correlation. The stability of these four bla NDM-1 tandem repeat structures was also investigated. This is the first documented case of bla NDM-1 tandem repeats in E. hormaechei, and the ISCR1 and other insertion sequence may play a role in this arrangement.

Keywords: Microbiology; Molecular biology.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Characterization of plasmids pL710hy-NDM-OXA (A) Plasmid characteristic of E. hormaechei L710hy. Southern blotting hybridization with blaNDM-1-specific probe is in region A. Plasmid size determination by S1-PFGE is in region B, with the marker Salmonella enterica serotype Braenderup H9812. (B) Sequence comparison analysis of pL710hy-NDM-OXA with pCFR17_1 (GenBank: CP035277), pOXA1_SCLZS47 (GenBank: CP092496), pC50_002 (GenBank: CP042480), and pMGH3_unnamed1 (GenBank: CP072954). Replication genes (repA2 and repFIB), antibiotic resistance genes (ARGs), and other elements are highlighted in green, blue, and red, respectively.
Figure 2
Figure 2
The genetic context of blaNDM-1 Comparison of genes surrounding blaNDM-1 on pL710hy-NDM-OXA, pEcNDM1, pNDM-IMP-1, and Tn125 in Acinetobacter baumannii. Open Reading Frames (ORFs) are shown as arrows and indicated according to their putative functions. Yellow indicates resistance gene blaNDM-1, blue indicates genes related to mobile elements, red represents other functional genes, and red box indicates 7,298 bp repeat unit of blaNDM-1. Regions with a high degree of homology are indicated by gray shading.
Figure 3
Figure 3
Putative mechanisms of the formation of the four blaNDM-1 tandem repeats
Figure 4
Figure 4
Comparison of the genetic environments of blaNDM-1 carried by pL710hy-NDM-OXA, L710hy-1, L710hy-11, L710hy-12, L710hy-20, and L710hy-92 ORFs are shown as arrows and labeled according to their putative function. Yellow indicates the resistance gene blaNDM-1, blue indicates genes associated with mobile elements, red indicates other functional genes, and red boxes indicate the 7,298 bp repeating unit of blaNDM-1. Regions with high homology are shaded in gray.
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