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Background <p>Despite the clinical importance of carbapenem-resistant <i>Citrobacter freundii</i> (CRCF), its resistance genomics is poorly understood. This study systematically characterizes the genomic features and evolution of clinical CRCF isolates, with detailed analysis of a <i>bla</i><sub>KPC−2</sub> and <i>bla</i><sub>NDM−1</sub> co-harboring strain.</p> Methods <p>Clinical CRCF isolates were collected from multiple tertiary hospitals in China, and their basic clinical data were obtained. Phenotypic characterization was performed through antimicrobial susceptibility testing and plasmid conjugation transfer assays. Bioinformatic analysis was conducted based on whole-genome sequencing data.</p> Results <p>Clinical data from 37 CRCF isolates in Zhejiang Province, China, revealed that infections primarily occurred among elderly patients (≥ 70 years, 65%) and in high-risk departments such as the ICU. The majority of isolates were recovered from urine samples (67%). Antimicrobial susceptibility testing indicated high resistance to carbapenems and most β-lactams, whereas susceptibility to amikacin remained moderate (21.6%) and no resistance against tigecycline and colistin was detected. Resistance mechanism analysis revealed that 97.3% of isolates carried <i>bla</i><sub>NDM</sub>, and <i>bla</i><sub>CMY</sub> was present in all strains. IncX3 (59.5%), IncFIB (54.1%), and IncFII (51.4%) were the predominant plasmid types. MLST identified 17 sequence types, with ST22 and ST116 being most prevalent. Both STs carried <i>bla</i><sub>NDM−1</sub>, clustered phylogenetically, and were persistently isolated from 2019 to 2024, indicating long-term clonal circulation. Complete genome analysis of a rare <i>bla</i><sub>KPC−2</sub> and <i>bla</i><sub>NDM−1</sub> co-harboring strain (T1001) confirmed that both genes were located on conjugative plasmids, with IS<i>26</i> and IS<i>Kpn19</i> facilitating their integration.</p> Conclusion <p>The dissemination of CRCF in Zhejiang Province, China, is driven by both clonal expansion of successful lineages (ST22, ST116) and horizontal transfer of resistance plasmids. These clones, persisting from 2019 to 2024, carry <i>bla</i><sub>NDM−1</sub> and show high carriage rates of IncX3 and IncFIB plasmids, suggesting a possible association between these replicon types and the dominant clones. Although amikacin, tigecycline, and colistin remain effective in vitro, the complex recombination mechanisms of resistance genes—particularly IS<i>26</i>/IS<i>Kpn19</i>-mediated modular dissemination—pose a serious nosocomial threat. Enhanced infection control measures are urgently needed to curb the spread of these multidrug-resistant bacteria and their resistance plasmids.</p>

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Comprehensive genomic analysis of carbapenem-resistant Citrobacter freundii and characterization of a co-carrying blaKPC−2 and blaNDM−1 isolate in Zhejiang Province， China

  • 期刊论文

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  • 发表日期：

    2026年5月8日

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  • Xinhua Luo,
  • Yali Zheng,
  • Jianbo Ye,
  • Jian Lan,
  • Huimin Chen,
  • Yuting Jin,
  • Jin Zhang,
  • Darong Duan

摘要

Background

Despite the clinical importance of carbapenem-resistant Citrobacter freundii (CRCF), its resistance genomics is poorly understood. This study systematically characterizes the genomic features and evolution of clinical CRCF isolates, with detailed analysis of a blaKPC−2 and blaNDM−1 co-harboring strain.

Methods

Clinical CRCF isolates were collected from multiple tertiary hospitals in China, and their basic clinical data were obtained. Phenotypic characterization was performed through antimicrobial susceptibility testing and plasmid conjugation transfer assays. Bioinformatic analysis was conducted based on whole-genome sequencing data.

Results

Clinical data from 37 CRCF isolates in Zhejiang Province, China, revealed that infections primarily occurred among elderly patients (≥ 70 years, 65%) and in high-risk departments such as the ICU. The majority of isolates were recovered from urine samples (67%). Antimicrobial susceptibility testing indicated high resistance to carbapenems and most β-lactams, whereas susceptibility to amikacin remained moderate (21.6%) and no resistance against tigecycline and colistin was detected. Resistance mechanism analysis revealed that 97.3% of isolates carried blaNDM, and blaCMY was present in all strains. IncX3 (59.5%), IncFIB (54.1%), and IncFII (51.4%) were the predominant plasmid types. MLST identified 17 sequence types, with ST22 and ST116 being most prevalent. Both STs carried blaNDM−1, clustered phylogenetically, and were persistently isolated from 2019 to 2024, indicating long-term clonal circulation. Complete genome analysis of a rare blaKPC−2 and blaNDM−1 co-harboring strain (T1001) confirmed that both genes were located on conjugative plasmids, with IS26 and ISKpn19 facilitating their integration.

Conclusion

The dissemination of CRCF in Zhejiang Province, China, is driven by both clonal expansion of successful lineages (ST22, ST116) and horizontal transfer of resistance plasmids. These clones, persisting from 2019 to 2024, carry blaNDM−1 and show high carriage rates of IncX3 and IncFIB plasmids, suggesting a possible association between these replicon types and the dominant clones. Although amikacin, tigecycline, and colistin remain effective in vitro, the complex recombination mechanisms of resistance genes—particularly IS26/ISKpn19-mediated modular dissemination—pose a serious nosocomial threat. Enhanced infection control measures are urgently needed to curb the spread of these multidrug-resistant bacteria and their resistance plasmids.