Molecular epidemiology and genomic characterization of a plasmid-mediated mcr-10 and blaNDM-1 co-harboring multidrug-resistant Enterobacter asburiae

Xinyang Li; Tian Jiang; Chenghao Wu; Yingying Kong; Yilei Ma; Jianyong Wu; Xinyou Xie; Jun Zhang; Zhi Ruan

doi:10.1016/j.csbj.2023.08.004

Molecular epidemiology and genomic characterization of a plasmid-mediated mcr-10 and bla_NDM-1 co-harboring multidrug-resistant Enterobacter asburiae

Comput Struct Biotechnol J. 2023 Aug 6:21:3885-3893. doi: 10.1016/j.csbj.2023.08.004. eCollection 2023.

Authors

Xinyang Li¹, Tian Jiang^{1

2}, Chenghao Wu¹, Yingying Kong^{1

3}, Yilei Ma^{1

3}, Jianyong Wu⁴, Xinyou Xie^{1

3}, Jun Zhang^{1

3}, Zhi Ruan^{1

3}

Affiliations

¹ Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Department of Clinical Laboratory, The Affiliated Wenling Hospital, Wenzhou Medical University, Taizhou, China.
³ Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, China.
⁴ Department of Clinical Laboratory, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China.

Abstract

Colistin is considered as one of the last-resort antimicrobial agents for treating multidrug-resistant bacterial infections. Multidrug-resistant E. asburiae has been increasingly isolated from clinical patients, which posed a great challenge for antibacterial treatment. This study aimed to report a mcr-10 and bla_NDM-1 co-carrying E. asburiae clinical isolate 5549 conferred a high-level resistance against colistin. Antibiotic susceptibility testing was performed using the microdilution broth method. Transferability of mcr-10 and bla_NDM-1-carrying plasmids were investigated by conjugation experiments. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to identify modifications in lipid A. Whole genome sequencing and phylogenetic analysis between strain 5549 and a total of 301 E. asburiae genomes retrieved from NCBI database were performed. The genetic characteristics of mcr-10 and bla_NDM-1-bearing plasmids were also analyzed. Our study indicated that strain 5549 showed extensively antibiotic-resistant trait, including colistin and carbapenem resistance. The mcr-10 and bla_NDM-1 were carried by IncFIB/IncFII type p5549_mcr-10 (159417 bp) and IncN type p5549_NDM-1 (63489 bp), respectively. Conjugation assays identified that only the bla_NDM-1-carrying plasmid could be successfully transferred to E. coli J53. Interestingly, mcr-10 did not mediate colistin resistance when it was cloned into E. coli DH5α. Mass spectrometry analysis showed the lipid A palmitoylation of the C-lacyl-oxo-acyl chain to the chemical structure of lipid A at m/z 2063 in strain 5549. In summary, this study is the first to report a mcr-10 and bla_NDM-1 co-occurrence E. asburiae recovered from China. Our investigation revealed the distribution of different clonal lineage of E. asburiae with epidemiology perspective and the underlying mechanisms of colistin resistance. Active surveillance is necessary to control the further dissemination of multidrug-resistant E. asburiae.

Keywords: Colistin resistance; Enterobacter asburiae; Lipid A; blaNDM-1; mcr-10.