Landscape of bla<sub>NDM</sub> genes in Enterobacteriaceae.
Yuta KikuchiHidehito MatsuiYukihiro AsamiAsaomi KuwaeYuki InahashiHideaki HanakiAkio AbePublished in: The Journal of antibiotics (2022)
The blaNDM-1 gene encodes a carbapenemase, New Delhi metallo-β-lactamase (NDM-1), and the ability to produce NDM-1 is spread among Enterobacteriaceae via horizontal gene transfer of plasmids. It has been widely accepted that bla<sub>NDM-1</sub> is regulated by a hybrid promoter (P<sub>ISAba125</sub>) consisting of a -10 box from the original bla<sub>NDM-1</sub> and a -35 box from ISAba125. However, the conservation of this promoter and the vertical transmission of bla<sub>NDM</sub> genes by chromosomal integration have not been comprehensively analyzed. We retrieved the region containing the ORF of bla<sub>NDM-1</sub> (>95% translated protein identity) and a region 120 bp upstream of the bla<sub>NDM-1</sub> start codon from the complete sequence data of Enterobacteriaceae plasmids (n = 10,914) and chromosomes (n = 4908) deposited in GenBank, and the 310 extracted bla<sub>NDM</sub> genes were analyzed by an in-silico approach. The results showed that most bla<sub>NDM</sub> genes (99.0%) utilized the promoter, P<sub>ISAba125</sub>. Interestingly, two bla<sub>NDM-1</sub> genes from the genus Citrobacter utilized the ISCR1-derived outward-oriented promoters P<sub>OUT</sub> (P<sub>ISCR1</sub>). Furthermore, the insertion of ISAba125 and ISCR1 occurred upstream of the CCATATTT sequence, which is located upstream of the -10 box. We also confirmed that most of the bla<sub>NDM</sub> genes were disseminated by horizontal gene transfer of the plasmid, but 10 cases of the bla<sub>NDM</sub> genes were integrated into the chromosome via mobile genetic elements such as IS26, IS150, ISCR1, ICE, and Tn7-like elements. Thus, plasmid-mediated transmission of the P<sub>ISAba125</sub>-bla<sub>NDM</sub> genes is predominant in Enterobacteriaceae. However, the spread of bla<sub>NDM</sub> genes with new promoters and vertical dissemination via chromosomal integrations may pose additional serious clinical problems.
Keyphrases
- klebsiella pneumoniae
- escherichia coli
- multidrug resistant
- genome wide
- genome wide identification
- transcription factor
- dna methylation
- copy number
- genome wide analysis
- bioinformatics analysis
- gram negative
- drug resistant
- acinetobacter baumannii
- binding protein
- cystic fibrosis
- big data
- single cell
- artificial intelligence