Genomic characterization of a carbapenem-resistant Citrobacter freundii cocarrying blaKPC-2 and blaNDM-1

Liu, Ying; Fang, Chengju; Qiu, Yichuan; Dai, Xiaoyi; Zhang, Luhua

doi:10.1016/j.jgar.2022.04.014

Cited by 9 publications

(6 citation statements)

References 7 publications

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“…JX104760), isolated from Klebsiella pneumonia in Hong Kong in 2011 [ 34 ]. The pNDM-HN380 plasmid has been reported in C. freundii , E. coli , and Enterobacter hormaechei [ 35 – 37 ], suggesting that plasmids harboring resistance genes are likely to be transmitted horizontally between different strains. Although IncX3 plasmids carrying bla NDM-1 have been frequently reported in other Citrobacter species [ 35 , 38 ], this is the first report in C. europaeus in China.…”

Section: Discussionmentioning

confidence: 99%

Whole-genome sequencing of clinical isolates of Citrobacter Europaeus in China carrying blaOXA−48 and blaNDM−1

Ma,

Xu,

et al. 2024

Ann Clin Microbiol Antimicrob

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Objective To analyze the clinical infection characteristics and genetic environments of resistance genes in carbapenem-resistant Citrobacter europaeus using whole-genome sequencing. Methods The susceptibility of two clinical isolates of C. europaeus (WF0003 and WF1643) to 24 antimicrobial agents was assessed using the BD Phoenix™ M50 System and Kirby-Bauer (K-B) disk-diffusion method. Whole-genome sequencing was performed on the Illumina and Nanopore platforms, and ABRicate software was used to predict resistance and virulence genes of carbapenem-resistant C. europaeus. The characteristics of plasmids carrying carbapenem-resistance genes and their genetic environments were analyzed. Single nucleotide polymorphisms were used to construct a phylogenetic tree to analyze the homology of these two C. europaeus strains with ten strains of C. europaeus in the NCBI database. Results The two strains of carbapenem-resistant C. europaeus are resistant to various antimicrobial agents, particularly carbapenems and β-lactams. WF0003 carries blaNDM− 1, which is located on an IncX3 plasmid that has high homology to the pNDM-HN380 plasmid. blaNDM− 1 is located on a truncated Tn125. It differs from Tn125 by the insertion of IS5 in the upstream ISAba125 and the deletion of the downstream ISAba125, which is replaced by IS26. WF1643 carries blaOXA− 48 in a Tn1999 transposon on the IncL/M plasmid, carrying only that single drug resistance gene. Homology analysis of these two strains of C. europaeus with ten C. europaeus strains in the NCBI database revealed that the 12 strains can be classified into three clades, with both WF0003 and WF1643 in the B clade. Conclusion To the best of our knowledge, this is the first study to report an IncX3 plasmid carrying blaNDM− 1 in C. europaeus in China. C. europaeus strains harboring carbapenem-resistance genes are concerning in relation to the spread of antimicrobial resistance, and the presence of carbapenem-resistance genes in C. europaeus should be continuously monitored.

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Section: Discussionmentioning

confidence: 99%

Whole-genome sequencing of clinical isolates of Citrobacter Europaeus in China carrying blaOXA−48 and blaNDM−1

Ma,

Xu,

et al. 2024

Ann Clin Microbiol Antimicrob

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“…CRCF coharboring bla KPC−2 and bla NDM−1 was first reported in 2015 (Feng et al, 2015 ) and has emerged continually in recent years, especially in China (Feng et al, 2015 ; Wu et al, 2016 ; Ouyang et al, 2018 ; Li et al, 2022 ). However, comprehensive analyses for the CRCF strains were lacking, and the potential dissemination mechanism has remained unclear.…”

Section: Discussionmentioning

confidence: 99%

“…To decipher the underlying mechanism in forming bla KPC−2and bla NDM−1 -coharboring CRCF strains, seven bla KPC−2 -and bla NDM−1 -coharboring CRCF strains having complete genomes, including three reported previously (Wu et al, 2016;Ouyang et al, 2018;Li et al, 2022) and four in this study, were analyzed (Figure 6). All were recovered in China after 2013 and could be divided into three clusters based on genome (cluster 1: CF26019; cluster 2: P10159 and WCHCF65; cluster 3: CF2075, CF2084, CF2085, and SCLZS47).…”

Section: Genome Analysis Of Bla Kpc--and Bla Ndm--coharboring Crcf St...mentioning

confidence: 99%

“…By comparison, the latter cannot hydrolyze monobactams and is unresponsive to the above β-lactamase inhibitors (Bush, 2013 ; Bush and Bradford, 2019 ). Importantly, bla KPC−2 - and bla NDM−1 -coproducing CPCF strains have been recovered from patient specimens and clinical waste in China, leading to limited options for antibacterial treatment (Feng et al, 2015 ; Wu et al, 2016 ; Ouyang et al, 2018 ; Li et al, 2022 ). Nevertheless, each of those studies only described a single CRCF strain carrying bla KPC−2 and bla NDM−1 on two separate plasmids.…”

Section: Introductionmentioning

confidence: 99%

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Carbapenem-resistant Citrobacter freundii harboring blaKPC−2 and blaNDM−1: a study on their transferability and potential dissemination via generating a transferrable hybrid plasmid mediated by IS6100

Zhang,

Li,

Liu

et al. 2023

Front. Microbiol.

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IntroductionThe increase in clinical Enterobacteriaceae with dual carbapenemase has become a serious healthcare concern. It is essential to characterize the transferability and potential dissemination of blaKPC−2- and blaNDM−1-coharboring carbapenem-resistant Citrobacter freundii (CRCF).MethodsFour blaKPC−2- and blaNDM−1-coharboring CRCF strains were collected from our surveillance of the prevalence of carbapenem-resistant Enterobacteriaceae. The isolates were assessed using species identification, antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing, plasmid stability, and fitness costs. Clonality, genome, plasmidome, and phylogeny were analyzed to reveal potential dissemination.ResultsThree ST523 blaKPC−2- and blaNDM−1-coharboring CRCF strains, collected from the same hospital within 1 month, exhibited high homology (both identity and coverage >99%), implying clonal dissemination and a small-scale outbreak. Moreover, the blaKPC−2 and blaNDM−1 genes were coharbored on an IncR plasmid, probably generated by a blaKPC−2-harboring plasmid acquiring blaNDM−1, in these three strains. Importantly, the IncR plasmid may form a transferable hybrid plasmid, mediated by IS6100 via transposition, with another IncFII plasmid included in the same C. freundii strain. Furthermore, the blaKPC−2 and blaNDM−1 of the fourth CRCF strain are located on two different non-transferable plasmids lacking complete transfer elements. Additionally, throughout the course of the 10-day continuous passage, the genetic surroundings of blaNDM−1 in four CRCF strains were gradually excised from their plasmids after the 8th day, whereas they maintained 100% retention for blaKPC−2. Genome and plasmidome analyses revealed that blaKPC−2- or blaNDM−1-harboring C. freundii were divergent, and these plasmids have high homology to plasmids of other Enterobacteriaceae.ConclusionClonal dissemination of ST523 blaKPC−2- and blaNDM−1-coharboring CRCF strains was detected, and we first reported blaKPC−2 and blaNDM−1 concomitantly located on one plasmid, which could be transferred with mediation by IS6100 via transposition. Continued surveillance should urgently be implemented.

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“…In recent years, the co-production of KPC and NDM (mainly KPC-2 and NDM-1) has become a severe threat to public health, with increasing reports worldwide, [7][8][9][10][11][12] and has been documented in other Enterobacteriaceae. [13][14][15] A nationwide survey in China revealed an increased prevalence of CRKP coproducing KPC-2 and NDM-1 in recent years. 16 According to previous reports, bla KPC and bla NDM are usually located on separate plasmids that can be transferred to new recipient bacteria through conjugation.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of a Novel Hybrid IncFIIpHN7A8:IncR:IncN Plasmid Co-Harboring blaNDM-5 and blaKPC-2 from a Clinical ST11 Carbapenem-Resistant Klebsiella pneumoniae Strain

Sun,

Chen,

et al. 2023

IDR

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Purpose We aimed to characterize a novel bla NDM-5 and bla KPC-2 co-carrying hybrid plasmid from a clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) strain. Methods Antimicrobial susceptibility was determined by the broth microdilution method. Plasmid size and localization were estimated using S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting. Plasmid transfer ability was evaluated by conjugation experiments. Whole genome sequencing (WGS) was performed using Illumina NovaSeq6000 and Oxford Nanopore MinION platforms. Genomic characteristics were analyzed using bioinformatics methods. Results Strain ZY27320 was a multidrug-resistant (MDR) clinical ST11 K. pneumoniae strain that confers high-level resistance to carbapenems (meropenem, MIC 128 mg/L; imipenem, MIC 64 mg/L) and ceftazidime/avibactam (MIC >128/4 mg/L). Both S1-PFGE–Southern blotting and whole genome sequencing revealed that the carbapenemase genes bla KPC-2 and bla NDM-5 were carried by the same IncFII pHN7A8 :IncR:IncN hybrid plasmid (pKPC2_NDM5). Conjugation experiments indicated that pKPC2_NDM5 was a non-conjugative plasmid. Conclusion This is the first report of a hybrid plasmid carrying both carbapenemase genes bla NDM-5 and bla KPC-2 in a clinical K. pneumoniae ST11 isolate that confers resistance to both ceftazidime/avibactam and carbapenems, thereby presenting a serious threat to treatment in clinical practice.

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Genomic characterization of a carbapenem-resistant Citrobacter freundii cocarrying blaKPC-2 and blaNDM-1

Cited by 9 publications

References 7 publications

Whole-genome sequencing of clinical isolates of Citrobacter Europaeus in China carrying blaOXA−48 and blaNDM−1

Whole-genome sequencing of clinical isolates of Citrobacter Europaeus in China carrying blaOXA−48 and blaNDM−1

Carbapenem-resistant Citrobacter freundii harboring blaKPC−2 and blaNDM−1: a study on their transferability and potential dissemination via generating a transferrable hybrid plasmid mediated by IS6100

Characterisation of a Novel Hybrid IncFIIpHN7A8:IncR:IncN Plasmid Co-Harboring blaNDM-5 and blaKPC-2 from a Clinical ST11 Carbapenem-Resistant Klebsiella pneumoniae Strain

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