Epidemiological characteristics and molecular features of carbapenem-resistant Enterobacter strains in China: a multicenter genomic study

ABSTRACT Epidemiological characteristics and molecular features of carbapenem-resistant Enterobacter (CR-Ent) species remain unclear in China. In this study, we performed a genomic study on 92 isolates from Enterobacter-caused infections from a multicenter study in China. Whole genome sequencing (WGS) was used to determine the genome sequence of 92 non-duplicated CR-Ent strains collected from multiple tertiary health centres. The precise species of Enterobacter strains were identified by average nucleotide identity (ANI) and in silico DNA–DNA hybridization (isDDH). Molecular features of high-risk CR-Ent sequence type (ST) lineages and carbapenemase-encoding plasmids were determined. The result revealed that the most common human-source CR-Ent species in China was E. xiangfangensis (66/92, 71.93%), and the proportion of carbapenemase-producing Enterobacter (CP-Ent) in CR-Ent was high (72/92, 78.26%) in comparison to other global regions. Furthermore, ST171 and ST116 E. xiangfangensis were the major lineages of CP-Ent strains, and ST171 E. xiangfangensis was more likely to cause infections in older patients. Genomic analysis also highlighted the likelihood of intra-hospital/inter-hospital clonal transmission of ST171 and ST116 E. xiangfangensis. In addition, the blaNDM-harbouring IncX3-type plasmid was identified as the prevalent carbapenemase-encoding plasmid carried by CR-Ent strains, and was experimentally confirmed to be able to self-transfer with high frequency. This study detailed the genomic and clinical characteristics of CR-Ent in China in the form of multicenter for the first time. The high risk of carbapenemase-producing ST171 and ST116 E. xiangfangensis, and the blaNDM-harbouring IncX3-type plasmid were detected and emphasized.

[1]  F. Balloux,et al.  Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene blaNDM , 2022, Nature communications.

[2]  Yuan Liu,et al.  Subinhibitory Concentration of Colistin Promotes the Conjugation Frequencies of Mcr-1- and blaNDM-5-Positive Plasmids , 2022, Microbiology spectrum.

[3]  W. van Schaik,et al.  Temperature-Regulated IncX3 Plasmid Characteristics and the Role of Plasmid-Encoded H-NS in Thermoregulation , 2022, Frontiers in Microbiology.

[4]  Zhiqiang Wang,et al.  Deciphering the Epidemiological Characteristics and Molecular Features of blaKPC–2- or blaNDM–1-Positive Klebsiella pneumoniae Isolates in a Newly Established Hospital , 2021, Frontiers in Microbiology.

[5]  Z. Zong,et al.  Carbapenem and Colistin Resistance in Enterobacter: Determinants and Clones. , 2021, Trends in microbiology.

[6]  Z. Zong,et al.  Precise Species Identification by Whole-Genome Sequencing of Enterobacter Bloodstream Infection, China , 2021, Emerging infectious diseases.

[7]  Robin Patel,et al.  Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study. , 2020, The Lancet. Infectious diseases.

[8]  P. Nordmann,et al.  Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria , 2019, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  A. Roberts,et al.  The Transposon Registry , 2019, Mobile DNA.

[10]  J. Pagés,et al.  Enterobacter spp.: Update on Taxonomy, Clinical Aspects, and Emerging Antimicrobial Resistance , 2019, Clinical Microbiology Reviews.

[11]  M. Adams,et al.  Genomic Epidemiology of Global Carbapenemase-Producing Enterobacter spp., 2008–2014 , 2018, Emerging infectious diseases.

[12]  Nora C. Toussaint,et al.  Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant Enterobacter cloacae Complex Clones ST171 and ST78 , 2018, mBio.

[13]  E. Snitkin,et al.  Genomic Investigation of a Putative Endoscope-Associated Carbapenem-Resistant Enterobacter cloacae Outbreak Reveals a Wide Diversity of Circulating Strains and Resistance Mutations , 2018, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[14]  R. Lynfield,et al.  A cluster of carbapenemase-producing Enterobacter cloacae complex ST171 at a tertiary care center demonstrating an ongoing regional threat. , 2019, American journal of infection control.

[15]  Wen J. Li,et al.  Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation , 2015, Nucleic Acids Res..

[16]  Fangfang Xia,et al.  RASTtk: A modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes , 2015, Scientific Reports.

[17]  Yong-ping Lin,et al.  Resistome Analysis of Enterobacter cloacae CY01, an Extensively Drug-Resistant Strain Producing VIM-1 Metallo-β-Lactamase from China , 2014, Antimicrobial Agents and Chemotherapy.

[18]  S. Stefani,et al.  Enterobacter cloacae complex: clinical impact and emerging antibiotic resistance. , 2012, Future microbiology.

[19]  S. Rasmussen,et al.  Identification of acquired antimicrobial resistance genes , 2012, The Journal of antimicrobial chemotherapy.

[20]  J. Schrenzel,et al.  Tn125-Related Acquisition of blaNDM-Like Genes in Acinetobacter baumannii , 2011, Antimicrobial Agents and Chemotherapy.

[21]  Patricia Siguier,et al.  ISfinder: the reference centre for bacterial insertion sequences , 2005, Nucleic Acids Res..

[22]  OUP accepted manuscript , 2021, Nucleic Acids Research.

[23]  I. Xenarios,et al.  UniProtKB/Swiss-Prot, the Manually Annotated Section of the UniProt KnowledgeBase: How to Use the Entry View. , 2016, Methods in molecular biology.