Abstract
Many antimicrobial resistance genes usually located on transferable plasmids are responsible for multiple antimicrobial resistance among multidrug-resistant (MDR) Gram-negative bacteria. The aim of this study is to characterize a carbapenemase-producing Enterobacter hormaechei 1575 isolate from the blood sample in a tertiary hospital in Wuhan, Hubei Province, China. Antimicrobial susceptibility test showed that 1575 was an MDR isolate. The whole genome sequencing (WGS) and comparative genomics were used to deeply analyze the molecular information of the 1575 and to explore the location and structure of antibiotic resistance genes. The three key resistance genes (blaSFO–1, blaNDM–1, and mcr-9) were verified by PCR, and the amplicons were subsequently sequenced. Moreover, the conjugation assay was also performed to determine the transferability of those resistance genes. Plasmid files were determined by the S1 nuclease pulsed-field gel electrophoresis (S1-PFGE). WGS revealed that p1575-1 plasmid was a conjugative plasmid that possessed the rare coexistence of blaSFO–1, blaNDM–1, and mcr-9 genes and complete conjugative systems. And p1575-1 belonged to the plasmid incompatibility group IncHI2 and multilocus sequence typing ST102. Meanwhile, the pMLST type of p1575-1 was IncHI2-ST1. Conjugation assay proved that the MDR p1575-1 plasmid could be transferred to other recipients. S1-PFGE confirmed the location of plasmid with molecular weight of 342,447 bp. All these three resistant genes were flanked by various mobile elements, indicating that the blaSFO–1, blaNDM–1, and mcr-9 could be transferred not only by the p1575-1 plasmid but also by these mobile elements. Taken together, we report for the first time the coexistence of blaSFO–1, blaNDM–1, and mcr-9 on a transferable plasmid in a MDR clinical isolate E. hormaechei, which indicates the possibility of horizontal transfer of antibiotic resistance genes.
Highlights
Carbapenem-resistant Enterobacteriaceae (CRE) has recently emerged as a serious threat to modern healthcare, challenging our present antibiotic treatment strategy (Chen et al, 2014)
The first plasmidmediated colistin resistance gene mcr-1 was identified in China from the plasmid of Escherichia coli and Klebsiella pneumoniae in IncI2 (Liu et al, 2016). mcr-1 remains the main plasmidmediated myxobacteria resistance gene, but mcr-2 to mcr-8 has been identified in different species in humans and animals (Wang et al, 2018; Nang et al, 2019). mcr-9 has been identified in Swedish ESBL isolates, including Enterobacter cloacae, E. coli, Klebsiella acidophilus, and Citrobacter freundii (Börjesson et al, 2020)
The spread of blaNDM-1 among bacterial pathogens is of concern because of resistance to carbapenems and because such pathogens typically are resistant to multiple antimicrobial drug classes, which leaves few treatment choices available (Kumarasamy et al, 2010; Moellering, 2010; Walsh, 2010)
Summary
Carbapenem-resistant Enterobacteriaceae (CRE) has recently emerged as a serious threat to modern healthcare, challenging our present antibiotic treatment strategy (Chen et al, 2014). The carbapenem-resistant and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are classified as the “priority pathogens” by the World Health Organization in 2017 (WHO, 2017; Tacconelli et al, 2018). Among all these Enterobacteriaceae isolates, Enterobacter hormaechei is a notorious nosocomial pathogen contributing to various infections, such as bacteremia, endocarditis, and lower respiratory, urinary tract, and intra-abdominal infections (Xu et al, 2015). The first plasmidmediated colistin resistance gene mcr-1 was identified in China from the plasmid of Escherichia coli and Klebsiella pneumoniae in IncI2 (Liu et al, 2016). Mobile colistin-resistant genes (mcr) have become an increasing public health concern
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