Coproduction of MCR-9 and NDM-1 by colistin-resistant enterobacter hormaechei isolated from bloodstream infection

Abstract

Background: Colistin acts as the last line of defense against severe infections caused by carbapenem-resistant Enterobacteriaceae. Infections caused by extensively drug-resistant isolates coproducing MCR and carbapenemases have posed a serious public health concern. Purpose: In this study, we reported the first clinical colistin and carbapenem-resistant Enterobacter hormaechei isolate SCNJ07 coharboring blaNDM-1 and mcr-9 from a patient with bloodstream infection in China. Methods: Bacterial antimicrobial susceptibility testing was performed using the broth microdilution method. Conjugation assay was carried out to investigate the transferability of mcr-9 and blaNDM-1. Whole-genome sequencing of strain SCNJ07 was performed using an Illumina HiSeq system and the genetic characteristics of the mcr-9-and blaNDM-1-harboring plasmids were analyzed. Results: Conjugation assays revealed that both blaNDM-1 and mcr-9 genes could successfully transfer their resistance phenotype to Escherichia coli strain J53. Whole genome sequencing showed that SCNJ07 possessed an FIB36:FIIY4 type self-transmissible plasmid bearing blaNDM-1, which possessed high similarity to previously reported pRJF866 in China. mcr-9 was located on a ~28-kb self-transmissible plasmid pMCR-SCNJ07 with both IncHI2 and IncR replicons. Two copies of intact IS903 that bracketed a ~8-kb region containing the mcr-9 gene were identified in pMCR-SCNJ07. BLASTn analysis revealed that a number of mcr-9-positive plasmids have been around for a while among Enterobacteriaceae worldwide. Conclusion: This study reveals the likelihood of a wide dissemination of this newly identified colistin resistance gene mcr-9 among Enterobacteriaceae. Further surveillance is urgently needed to understand the prevalence and dissemination of mcr-9, thereby facilitating establishment of measures to control its spread.