Coproduction Of MCR-9 And NDM-1 By Colistin-Resistant Enterobacter hormaechei Isolated From Bloodstream Infection

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 bla(NDM-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 bla(NDM-1). Whole-genome sequencing of strain SCNJ07 was performed using an Illumina HiSeq system and the genetic characteristics of the mcr-9- and bla(NDM-1)-harboring plasmids were analyzed. Results: Conjugation assays revealed that both bla(NDM-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 bla(NDM-1), which possessed high similarity to previously reported pRJF866 in China. mcr-9 was located on a similar to 28-kb self-transmissible plasmid pMCR-SCNJ07 with both IncHI2 and IncR replicons. Two copies of intact IS903 that bracketed a similar to 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.