Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring Citrobacter freundii in China with an IncR plasmid
Year: 2024
Type: article
Abstract: ABSTRACT The rise of carbapenem-resistant Enterobacteriaceae coharboring KPC-2 and NDM-1 poses a significant public health threat. KPC-2-NDM-1- Citrobacter freundii is rarely reported in clinical settings. In this study, we report the largest cohort of eight KPC-2-NDM-1- C. freundii isolated from children with urinary tract infections. Comprehensive characterization, including antimicrobial susceptibility testing, plasmid conjugation, whole-genome sequencing, and comparative genomics, was conducted for these clinical strains. Antimicrobial susceptibility testing indicated that all strains were resistant to meropenem [minimal inhibitory concentration (MICs) ≥ 8 µg/mL] and imipenem (MICs > 8 µg/mL). Genotyping and comparative genomics analyses identified the eight KPC-2-NDM-1- C. freundii belonging to ST523, exhibiting a close relationship characterized by 45 single nucleotide polymorphisms. Whole-genome sequencing and plasmid analysis confirmed the presence of bla KPC-2 and bla NDM-1 on an IncR plasmid named pC275-2 with 46,050 bp. The bla NDM-1 was integrated within the bla NDM-1 related region, which includes ΔIS Aba125 , bla NDM-1 , ble-MBL , trpF , dsbD , and IS CR1 , while the bla KPC-2 gene was located on a novel non-Tn 4401 genetic element. The bla KPC-2 genetic architectures containing bla KPC-2 differed from classical structures, underscoring the ongoing evolution of these genetic elements. IMPORTANCE Our study described the largest cohort to date of eight ST523 KPC-2-NDM-1- C. freundii isolated from children with urinary tract infections. The cooccurrence of KPC-2, a serine β -lactamases, and NDM-1, a metallo-β-lactamase on an IncR plasmid pC275-2 from a clinical carbapenem-resistant C . freundii . The conserved insertion structure mediated the bla NDM-1 , and the propagation of bla KPC-2 gene with a new genetic background using IncR plasmid in clinical settings promotes the emergence of superbugs necessitating vigilant monitoring. Our research detected that ST523 KPC-2- NDM-1- C. freundii were disseminated in a children’s hospital. The potential spread of an IncR plasmid within the hospital raises concerns about the pandemic potential of this clone that produces two carbapenemases: KPC-2 and NDM-1. Further investigations will be necessary to control and prevent the spread of KPC-2-NDM-1- C. freundii s.
Source: Microbiology Spectrum
Institutions: Zhengzhou University, Zhengzhou Children's Hospital
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W4405570386