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Updated: Mar 3, 2026
Isolation and Identification of Waterborne Antibiotic-Resistant Bacteria and Molecular Characterization of their Antibiotic Resistance Genes
Published on: March 3, 2023
Molecular mechanisms and clonal distribution of cefiderocol-resistant blaNDM-carrying Escherichia coli: A
Chengkang Tang1, Siquan Shen2, Renru Han2
1Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China; Department of Laboratory Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Reports on cefiderocol resistance are increasing globally despite its unavailability in China. The blaNDM-carrying Escherichia coli was one of the most frequent pathogens mediating cefiderocol resistance.
Objective:
More systematic resistance mechanisms and potential resistance distribution in the NDM-producing E. coli strains isolated in China require further investigation.
Methods:
We detected the cefiderocol susceptibility of 1,079 common Gram-negative bacteria collected nationwide. Of these, 95 blaNDM-carrying E. coli strains were selected for further study. A series of experiments and bioinformatics analysis were performed to study the resistance mechanisms and the epidemiological distribution of blaNDM-carrying E. coli.
Results:
Cefiderocol exhibited potent antibacterial activity against most strains (susceptibility rates were all > 75%) except for blaNDM-carrying E. coli with resistance rate as high as 50.5% (48/95). High-level cefiderocol resistance was attributed to the synergies of multiple mechanisms (blaNDM production and CirA-frameshift mutation/PBP3 insertion). Growth curve showed CirA/PBP3 mutants imposed no additional fitness cost. Among these strains, a total of 20 homologous strains were found, suggesting possible clonal transmission and hospital outbreak. Further study on the blaNDM-carrying E. coli isolated in China during 2021-2024 combined with NCBI database showed that resistance related CirA/PBP3 mutations (CirA-frameshift mutations/I547F and PBP3-Q227H, YRIN333ins, E349K, I532L) were usually co-occurring and concentrated in certain lineages. The diverse source suggested the potential humans-animals-environment spread of resistant strains. Furthermore, the genetic distribution of these potential resistant isolates was associated with their geographical origins.
Conclusion:
Our study revealed high cefiderocol resistance rates among blaNDM-carrying E. coli isolates in China. More importantly, the molecular mechanisms and potential dissemination of cefiderocol-resistant blaNDM-carrying E. coli were determined to underline the urgency for the 'One Health' strategy and provide a reference for its future use in China.
