Molecular characterization of a carbapenem-resistant Enterobacter hormaechei ssp. xiangfangensis co-harbouring blaNDM-1 and a chromosomally encoded phage-linked blaCTX-M-15 genes

Abstract

Enterobacter cloacae complex (ECC) members are rapidly emerging as successful nosocomial pathogens, especially, with the emergence of carbapenem-resistant clones. In this study, we performed a comprehensive molecular characterization of a carbapenem-resistant E. hormaechei ssp. xiangfangensis LAU_ENC1. hsp60 and average nucleotide identity (ANI) were used for its identification. The repertoire of resistance genes and phage content were analyzed. Plasmid sequences were extracted and compared to closest references. The isolate LAU_ENC1 was identified as an E. hormaechei ssp. xiangfangensis and belonged to ST-114A sub-cluster. bla_NDM-1, bla_CTX-M-15, bla_OXA-1, and bla_ACT-16 genes were detected as β-lactam resistance determinants. A chromosomal hybrid intact phage, Enterobacter phage LAU1, with bla_CTX-M-15 integrated in its direct vicinity within an ISEcp1 - bla_CTX-M-15 - wbuC - ∆Tn2 rare cassette was detected. bla_NDM-1 was integrated within a novel IncFII conjugative plasmid, pLAU_ENC1, through an IS3000- ΔISAba125-bla_NDM-1-ble_MBL-//-Tn5403 cassette. To our knowledge, this is the first report of a multi-drug resistant (MDR) E. hormaechei ssp. xiangfangensis carrying a bla_CTX-M-15 integrated within the proximity of a provirus chromosomal region. Treatment options for MDR ECC members are becoming scarce, thus warranting an increased monitoring of the dissemination of these pathogens in clinical settings.

Keywords: Bacteriophage; CR-Enterobacteriaceae; ESBL; Plasmid.