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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.


ABSTRACT:

Introduction

The 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).

Methods

Four 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.

Results

Three 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.

Conclusion

Clonal 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.

SUBMITTER: Zhang F 

PROVIDER: S-EPMC10469622 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Carbapenem-resistant <i>Citrobacter freundii</i> harboring <i>bla</i><sub>KPC-2</sub> and <i>bla</i><sub>NDM-1</sub>: a study on their transferability and potential dissemination via generating a transferrable hybrid plasmid mediated by IS<i>6100</i>.

Zhang Feilong F   Li Ziyao Z   Liu Xinmeng X   Hu Yanning Y   Zhao Jiankang J   Zhang Yulin Y   Fan Yanyan Y   Lei Zichen Z   Yang Xinrui X   Li Zhihua Z   Li Chen C   Wu Yongli Y   Lu Binghuai B  

Frontiers in microbiology 20230817


<h4>Introduction</h4>The increase in clinical <i>Enterobacteriaceae</i> with dual carbapenemase has become a serious healthcare concern. It is essential to characterize the transferability and potential dissemination of <i>bla</i><sub>KPC-2</sub>- and <i>bla</i><sub>NDM-1</sub>-coharboring carbapenem-resistant <i>Citrobacter freundii</i> (CRCF).<h4>Methods</h4>Four <i>bla</i><sub>KPC-2</sub>- and <i>bla</i><sub>NDM-1</sub>-coharboring CRCF strains were collected from our surveillance of the prev  ...[more]

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