Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring Citrobacter freundii in China with an IncR plasmid
ABSTRACT The rise of carbapenem-resistant Enterobacteriaceae coharboring KPC-2 and NDM-1 poses a significant public health threat. KPC-2-NDM-1-Citrobacter freundii is rarely reported in clinical settings. In this study, we report the largest cohort of eight KPC-2-NDM-1-C. freundii isolated from chil...
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American Society for Microbiology
2025-02-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01953-24 |
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| author | Juanjuan Zhou Minghui Zhen Kaijie Gao Lu Xu Dongyu Zhang Junmei Yang |
| author_facet | Juanjuan Zhou Minghui Zhen Kaijie Gao Lu Xu Dongyu Zhang Junmei Yang |
| author_sort | Juanjuan Zhou |
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| description | ABSTRACT The rise of carbapenem-resistant Enterobacteriaceae coharboring KPC-2 and NDM-1 poses a significant public health threat. KPC-2-NDM-1-Citrobacter freundii is rarely reported in clinical settings. In this study, we report the largest cohort of eight KPC-2-NDM-1-C. freundii isolated from children with urinary tract infections. Comprehensive characterization, including antimicrobial susceptibility testing, plasmid conjugation, whole-genome sequencing, and comparative genomics, was conducted for these clinical strains. Antimicrobial susceptibility testing indicated that all strains were resistant to meropenem [minimal inhibitory concentration (MICs) ≥ 8 µg/mL] and imipenem (MICs > 8 µg/mL). Genotyping and comparative genomics analyses identified the eight KPC-2-NDM-1- C. freundii belonging to ST523, exhibiting a close relationship characterized by 45 single nucleotide polymorphisms. Whole-genome sequencing and plasmid analysis confirmed the presence of blaKPC-2 and blaNDM-1 on an IncR plasmid named pC275-2 with 46,050 bp. The blaNDM-1 was integrated within the blaNDM-1 related region, which includes ΔISAba125, blaNDM-1, ble-MBL, trpF, dsbD, and ISCR1, while the blaKPC-2 gene was located on a novel non-Tn4401 genetic element. The blaKPC-2 genetic architectures containing blaKPC-2 differed from classical structures, underscoring the ongoing evolution of these genetic elements.IMPORTANCEOur study described the largest cohort to date of eight ST523 KPC-2-NDM-1-C. freundii isolated from children with urinary tract infections. The cooccurrence of KPC-2, a serine β-lactamases, and NDM-1, a metallo-β-lactamase on an IncR plasmid pC275-2 from a clinical carbapenem-resistant C. freundii. The conserved insertion structure mediated the blaNDM-1, and the propagation of blaKPC-2 gene with a new genetic background using IncR plasmid in clinical settings promotes the emergence of superbugs necessitating vigilant monitoring. Our research detected that ST523 KPC-2- NDM-1-C. freundii were disseminated in a children’s hospital. The potential spread of an IncR plasmid within the hospital raises concerns about the pandemic potential of this clone that produces two carbapenemases: KPC-2 and NDM-1. Further investigations will be necessary to control and prevent the spread of KPC-2-NDM-1-C. freundiis. |
| format | Article |
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| institution | Kabale University |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-058bffeb0f6e4911bf490a99746fe3152025-02-04T14:03:40ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-02-0113210.1128/spectrum.01953-24Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring Citrobacter freundii in China with an IncR plasmidJuanjuan Zhou0Minghui Zhen1Kaijie Gao2Lu Xu3Dongyu Zhang4Junmei Yang5Department of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, ChinaDepartment of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, ChinaDepartment of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, ChinaDepartment of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, ChinaDepartment of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, ChinaDepartment of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, ChinaABSTRACT The rise of carbapenem-resistant Enterobacteriaceae coharboring KPC-2 and NDM-1 poses a significant public health threat. KPC-2-NDM-1-Citrobacter freundii is rarely reported in clinical settings. In this study, we report the largest cohort of eight KPC-2-NDM-1-C. freundii isolated from children with urinary tract infections. Comprehensive characterization, including antimicrobial susceptibility testing, plasmid conjugation, whole-genome sequencing, and comparative genomics, was conducted for these clinical strains. Antimicrobial susceptibility testing indicated that all strains were resistant to meropenem [minimal inhibitory concentration (MICs) ≥ 8 µg/mL] and imipenem (MICs > 8 µg/mL). Genotyping and comparative genomics analyses identified the eight KPC-2-NDM-1- C. freundii belonging to ST523, exhibiting a close relationship characterized by 45 single nucleotide polymorphisms. Whole-genome sequencing and plasmid analysis confirmed the presence of blaKPC-2 and blaNDM-1 on an IncR plasmid named pC275-2 with 46,050 bp. The blaNDM-1 was integrated within the blaNDM-1 related region, which includes ΔISAba125, blaNDM-1, ble-MBL, trpF, dsbD, and ISCR1, while the blaKPC-2 gene was located on a novel non-Tn4401 genetic element. The blaKPC-2 genetic architectures containing blaKPC-2 differed from classical structures, underscoring the ongoing evolution of these genetic elements.IMPORTANCEOur study described the largest cohort to date of eight ST523 KPC-2-NDM-1-C. freundii isolated from children with urinary tract infections. The cooccurrence of KPC-2, a serine β-lactamases, and NDM-1, a metallo-β-lactamase on an IncR plasmid pC275-2 from a clinical carbapenem-resistant C. freundii. The conserved insertion structure mediated the blaNDM-1, and the propagation of blaKPC-2 gene with a new genetic background using IncR plasmid in clinical settings promotes the emergence of superbugs necessitating vigilant monitoring. Our research detected that ST523 KPC-2- NDM-1-C. freundii were disseminated in a children’s hospital. The potential spread of an IncR plasmid within the hospital raises concerns about the pandemic potential of this clone that produces two carbapenemases: KPC-2 and NDM-1. Further investigations will be necessary to control and prevent the spread of KPC-2-NDM-1-C. freundiis.https://journals.asm.org/doi/10.1128/spectrum.01953-24Citrobacter freundiiKPC-2-NDM-1-CRCFsdisseminationcomparative genomic analysis |
| spellingShingle | Juanjuan Zhou Minghui Zhen Kaijie Gao Lu Xu Dongyu Zhang Junmei Yang Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring Citrobacter freundii in China with an IncR plasmid Microbiology Spectrum Citrobacter freundii KPC-2-NDM-1-CRCFs dissemination comparative genomic analysis |
| title | Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring Citrobacter freundii in China with an IncR plasmid |
| title_full | Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring Citrobacter freundii in China with an IncR plasmid |
| title_fullStr | Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring Citrobacter freundii in China with an IncR plasmid |
| title_full_unstemmed | Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring Citrobacter freundii in China with an IncR plasmid |
| title_short | Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring Citrobacter freundii in China with an IncR plasmid |
| title_sort | emergence and clonal dissemination of kpc 2 and ndm 1 coharboring citrobacter freundii in china with an incr plasmid |
| topic | Citrobacter freundii KPC-2-NDM-1-CRCFs dissemination comparative genomic analysis |
| url | https://journals.asm.org/doi/10.1128/spectrum.01953-24 |
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