Transmission of Nonconjugative Virulence or Resistance Plasmids Mediated by a Self-Transferable IncN3 Plasmid from Carbapenem-Resistant Klebsiella pneumoniae

Wang, Xiaoli; Tang, Bin; Liu, Guitian; Wang, Meng; Sun, Jingyong; Tan, Ruoming; Pan, Tingting; Qu, Jieming; Liu, Jialin; Ou, Hong‐Yu; Qu, Hongping

doi:10.1128/spectrum.01364-22

Cited by 9 publications

(4 citation statements)

References 45 publications

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“…Sequence analysis indicated that pCfr_tK-N was a recombinant of pCF2075-1 and pCF2075-2 mediated by IS 6100 , and this intermolecular transposition was first reported. Similar recombination, mediated by IS 26 , IS Kpn14 , IS Kpn74 , and IS 903B , was also reported in conjugations among different resistant or virulent plasmids in recent years, which could accelerate the dissemination of resistance and virulence genes (Wang et al, 2022a , b ; Yang et al, 2022 ). The pCF2075-1 being transferred by generating recombinants might be explained by the fact that the self-transferrable plasmids usually contain four modules: origin of transfer site oriT , relaxase gene, gene encoding type IV coupling protein (T4CP), and gene cluster for bacterial type IV secretion system (T4SS).…”

Section: Discussionsupporting

confidence: 57%

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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Section: Discussionsupporting

confidence: 57%

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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“…It is worth noting that we observed extensive fragment plasmid fusions in two non-conjugative MDR and virulence plasmids contributed by several transposases. Due to the presence of various mobile elements in both MDR and virulence plasmids, we speculate that these plasmids have a high potential to fuse with other conjugative plasmids and form conjugative MDR and virulence-encoding plasmids, facilitating transmission of virulence plasmid to different types of K. pneumoniae strains ( Xie et al., 2020 ; Wang et al., 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Outbreak of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae ST15 in a Chinese teaching hospital: a molecular epidemiological study

Wu,

Li,

et al. 2023

Front. Cell. Infect. Microbiol.

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Background and AimsThe incidence of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae (CRKP) has been on the rise in China over the past five years, potentially leading to nosocomial epidemics. This study investigates the first outbreak of CRKP in the Second Affiliated Hospital of Jiaxing University.MethodsBetween February 2021 and March 2022, 21 clinical isolates of OXA-232-producing CRKP were recovered from 16 patients in the Second Affiliated Hospital of Jiaxing University. We conducted antimicrobial susceptibility tests, whole genome sequencing, and bioinformatics to determine the drug resistance profile of these clinical isolates.ResultsWhole-genome sequencing revealed that all 21 OXA-232-producing CRKP strains belonged to the sequence type 15 (ST15) and shared similar resistance, virulence genes, and plasmid types, suggesting clonal transmission between the environment and patients. Integrated genomic and epidemiological analysis traced the outbreak to two clonal transmission clusters, cluster 1 and cluster 2, including 14 and 2 patients. It was speculated that the CRKP transmission mainly occurred in the ICU, followed by brain surgery, neurosurgery, and rehabilitation department. Phylogenetic analysis indicated that the earliest outbreak might have started at least a year before the admission of the index patient, and these strains were closely related to those previously isolated from two major adjacent cities, Shanghai and Hangzhou. Comparative genomics showed that the IncFII-type and IncHI1B-type plasmids of cluster 2 had homologous recombination at the insertion sequence sites compared with the same type of plasmids in cluster 1, resulting in the insertion of 4 new drug resistance genes, including TEM-1, APH(6)-Id, APH(3’’)-Ib and sul2.ConclusionsOur study observed the clonal spread of ST15 OXA-232-producing between patients and the hospital environment. The integration of genomic and epidemiological data offers valuable insights and facilitate the control of nosocomial transmission.

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“…19,54,63 Despite their limitation in conjugation transfer, nontransmissible IncR plasmids can serve as a reservoir by fusion with other types of resistance plasmids or directly cotransfer with the helper self-transferable IncN3 plasmid, thereby enhancing its ability to transmit to other K. pneumoniae lineage or Enterobacteriaceae species. 70,71 More importantly, recent studies reminded the public that strains with this plasmid became high virulence and multidrug resistances. 61,66,[72][73][74] In this study, the tra regions in the three sequenced plasmids were incomplete compared with that in pHN7A8 and the bla KPC-2 gene was only detected in ST11, suggesting a limited horizontal transmission of this plasmid.…”

Section: Discussionmentioning

confidence: 99%

Tandem Repeat of blaNDM-1 and Clonal Dissemination of a fosA3 and blaKPC-2 Co-Carrying IncR-F33: A–: B– Plasmid in Klebsiella pneumoniae Isolates Collected in a Southwest Hospital in China, 2010–2013

Hu¹,

Zhang²,

Shen³

et al. 2022

IDR

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Introduction Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been widespread in coastal cities of eastern China since 2009. However, how CRKP spreads and evolves in southwest China is unclear. Aim We investigated the genetic characteristics and dissemination mechanisms of carbapenemase genes in forty-one non-repetitive CRKP isolates collected from a southwest hospital, Kunming, Yunnan, during 2010–2013. Methodology Drug susceptibilities were analyzed by using VITEK 2 compact system. Genetic relationships were ascertained based on multilocus sequence typing (MLST) and Pulsed-field gel electrophoresis (PFGE) analysis. Genetic backgrounds of bla KPC-2 and bla NDM-1 were revealed by DNA walking and high-throughput sequencing. Results All isolates were highly resistant to common antibiotics except for tigecycline. In total, 34 bla KPC-2 , 3 bla NDM-1 , 1 bla IMP-4 and 3 bla IMP-26 genes were identified and KP67 plasmid 1 co-harbored bla NDM-1 and bla IMP-26 . Five sequence types, namely ST11, ST290, ST340, ST395 and ST437, were recognized by MLST. Surprisingly, bla KPC-2 was only detected in ST11 strains. We described a clonal dissemination of fosA3 -positive IncR-IncF33:A-:B- multireplicon plasmid carrying the gene cassettes IS 26 -ΔTn 3 -IS Kpn27-bla KPC-2 -ΔIS Kpn6-korC-klcA -Δ repB -Tn 1721 in all ST11 isolates. Three bla NDM-1 positive isolates belonged to three different ST types and their bla NDM-1 genetic backgrounds were also distinct. Interestingly, the flanking regions of bla NDM-1 in KP67 and KP72 were duplicated into one to five copies in a form of tandem repeat by the transposition of IS 91 like element. The bla NDM-1 of KP82 was carried on a common IncX3 plasmid. Conclusion This study described the early epidemiological characteristics of bla KPC-2 / bla NDM-1 -carrying CRKP, and reported a new tandem repeat pattern of bla NDM-1 cluster in Yunnan. These findings extend our knowledge on the carbapenemase gene evolutions.

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Transmission of Nonconjugative Virulence or Resistance Plasmids Mediated by a Self-Transferable IncN3 Plasmid from Carbapenem-Resistant Klebsiella pneumoniae

Cited by 9 publications

References 45 publications

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

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

Outbreak of OXA-232-producing carbapenem-resistant Klebsiella pneumoniae ST15 in a Chinese teaching hospital: a molecular epidemiological study

Tandem Repeat of blaNDM-1 and Clonal Dissemination of a fosA3 and blaKPC-2 Co-Carrying IncR-F33: A–: B– Plasmid in Klebsiella pneumoniae Isolates Collected in a Southwest Hospital in China, 2010–2013

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