Co-Occurrence of mcr-9 and bla NDM-1 in Enterobacter cloacae Isolated from a Patient with Bloodstream Infection

摘要

Background: Bloodstream infection (BSI) caused by carbapenem-resistant Enterobacteriaceae are potentially life-threatening related to poorer outcomes. Colistin is considered one of the last-resort treatments against human infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Therefore, emergence of strains from the blood that co-harboring mcr and carbapenem resistance genes were considered as a serious problem. Purpose: In this study, two mcr-9 -harboring MDR Enterobacter cloacae isolates BSI034 and BSI072 recovered from BSI patients were identified, one of which co-harbored mcr-9 and bla subNDM-1./sub The genetic characteristics of the MDR plasmid needed to be clarified. Methods: S1-PFGE and Southern blotting were conducted to determine the location of mcr-9 . Whole-genome sequencing was performed to obtain the complete genome and plasmid sequences. The resistome and virulence genes of the strains, accompanied by the genetic characteristics of mcr-9 - and bla subNDM-1/sub-harboring plasmids, were analyzed. Results: Whole-genome sequencing showed that BSI034 harbored mcr-9 -carrying IncHI2-type pBSI034-MCR9 and bla subNDM-1/sub-carrying IncX3-type pBSI034-NDM1. The 278,517 bp pBSI034-MCR9 carried mcr-9 along with the other 19 resistance genes. mcr-9 was flanked by IS 903B (1057 bp) and IS 26 (820 bp) in the same orientation. In addition to resistance genes, strain BSI034 also carried a chromosome-located Yersinia high-pathogenicity island, which harbored genes of yersiniabactin biosynthesis operon ybtSXQPAUTE, irp1/2 , and fyuA . Conclusion: We described the complete genome and mcr-9 / bla subNDM-1/sub-co-harboring plasmid of E. cloacae from a BSI patient. Notable differences were observed within mosaic modules between pBSI034-MCR9 and other mcr-9 -harboring plasmids due to extensive recombination via horizontal gene transfer.