Abstract
BackgroundThe spread of Enterobacteriaceae producing both carbapenemases and Mcr, encoded by plasmid-mediated colistin resistance genes, has become a serious public health problem worldwide. This study describes three clinical isolates of Enterobacter cloacae complex co-harboring blaIMP-1 and mcr-9 that were resistant to carbapenem but susceptible to colistin.MethodsThirty-two clinical isolates of E. cloacae complex non-susceptible to carbapenems were obtained from patients at 14 hospitals in Japan. Their minimum inhibitory concentrations (MICs) were determined by broth microdilution methods and E-tests. Their entire genomes were sequenced by MiSeq and MinION methods. Multilocus sequence types were determined and a phylogenetic tree constructed by single nucleotide polymorphism (SNP) alignment of whole genome sequencing data.ResultsAll 32 isolates showed MICs of ≥2 μg/ml for imipenem and/or meropenem. Whole-genome analysis revealed that all these isolates harbored blaIMP-1, with three also harboring mcr-9. These three isolates showed low MICs of 0.125 μg/ml for colistin. In two of these isolates, blaIMP-1 and mcr-9 were present on two separate plasmids, of sizes 62 kb and 280/290 kb, respectively. These two isolates did not possess a qseBC gene encoding a two-component system, which is thought to regulate the expression of mcr-9. In the third isolate, however, both blaIMP-1 and mcr-9 were present on the chromosome.ConclusionThe mcr-9 is silently distributed among carbapenem-resistant E. cloacae complex isolates, of which are emerging in hospitals in Japan. To our knowledge, this is the first report of isolates of E. cloacae complex harboring both blaIMP-1 and mcr-9 in Japan.
Highlights
The spread of Enterobacteriaceae producing both carbapenemases and Mcr, encoded by plasmidmediated colistin resistance genes, has become a serious public health problem worldwide
Colistin resistance has been associated with modification of the lipid A moiety in lipopolysaccharide, such as by the addition of 4-amino-4-deoxy-L-arabinose (L-Ara-4 N) and phosphoethanolamine (PEtN) to the anionic phosphate groups of lipid A
This is the first report of isolates of E. cloacae complex harboring both blaIMP-1 and mcr-9 in Japan
Summary
The spread of Enterobacteriaceae producing both carbapenemases and Mcr, encoded by plasmidmediated colistin resistance genes, has become a serious public health problem worldwide. Colistin resistance has been associated with modification of the lipid A moiety in lipopolysaccharide, such as by the addition of 4-amino-4-deoxy-L-arabinose (L-Ara-4 N) and phosphoethanolamine (PEtN) to the anionic phosphate groups of lipid A. These additions reduce the anionic charges on lipid A and its affinity to the cationic colistin, inhibiting membrane destruction resulting from the binding of colistin to lipid A, followed by cell death [8]
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