Co-occurrence of mcr-9 and blaNDM-5 in Multidrug-Resistant Enterobacter hormaechei Strain Isolated from a Patient with Bloodstream Infection.

Abstract

Enterobacter hormaechei (E. hormaechei), a member of the Enterobacter cloacae complex, has emerged as an important pathogen in healthcare-associated infections. In this study, a multidrug-resistant E. hormaechei EH001 co-carrying mcr-9 and bla_NDM-5 was isolated from a patient with bloodstream infection in China. To investigate the genomic characteristics of a multidrug-resistant E. hormaechei EH001 co-carrying mcr-9 and bla_NDM-5, whole-genome sequencing was employed and conjugation experiment was performed by using the recipient E. coli EC600. The antimicrobial susceptibility profiles of E. hormaechei EH001 revealed resistance to the most commonly used antimicrobial agents, with the exception of polymyxin B, polymyxin E, and minocycline. E. hormaechei EH001 was classified as sequence type 78 (ST78) and harbored multiple resistance genes, especially co-carried mcr-9 and bla_NDM-5 located on an IncHI2 plasmid (pMCR9_EH001) and an IncX3 plasmid (pNDM5_EH001), respectively. Both plasmids were successfully co-transferred to E. coli EC600 by conjugation. Analysis of the genetic environment of mcr-9 and bla_NDM-5 revealed the multiple mobile genetic elements, such as insertion sequences (IS) and transposon (Tn). ∆Tn3-IS3000-∆ISAba125-5'-IS5-∆ISAba125-3' were situated upstream of bla_NDM-5, while ble_MBL-trpF-dsbD-CutA-IS26 were situated downstream of it. In addition, rcnR, rcnA, pcoE, pcoS, and IS5 family transposase (IS903B) were situated upstream of mcr-9, while IS3000 was situated downstream of it, followed by bla_CTX-M-3 and IS26. The majority of the plasmid-mediated resistance genes reside within or adjacent to diverse mobile genetic elements, which may potentially promote the horizontal transfer of antibiotic resistance determinants. This study represents the initial investigation providing the detailed genomic characteristics associated with co-occurrence of mcr-9 and bla_NDM-5 in E. hormaechei. The findings advocate for heightened clinical vigilance toward such strains, particularly to prevent nosocomial transmission.