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Peer-reviewedCC BY 4.0Antibiotics

Reduced susceptibility to cefiderocol among clinical MCR-1-producing Escherichia coli isolates from Tunisia

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Abstract

Background/Objectives: The emergence of plasmid-mediated mcr genes has enabled horizontal dissemination of resistance to colistin, a last-resort antibiotic against multidrug-resistant Enterobacterales. In Tunisia, genomic data on mcr-positive Escherichia coli are still limited. This study reports the genomic characterization of human clinical mcr-positive E. coli isolates from the Military Hospital of Tunis. Methods: Between August 2023 and March 2025, seven E. coli isolates with low-level colistin-resistance (MIC = 4–8 µg/mL) were collected from six patients. They were characterized by antibiotic susceptibility testing and WGS to determine resistome, MLST, genetic relatedness, and plasmid content. Results: The E. coli isolates belonged to diverse sequence types (STs), except for two isolates collected from the same patient 2.5 months apart, which were highly related. Overall, this pattern is consistent with a polyclonal spread. The mcr-1.1 gene was located on IncI2 (n = 5) or IncX4 (n = 2) plasmids, which exhibited high similarity both among themselves and in comparison with plasmids previously reported in human and livestock isolates. Most isolates were multidrug-resistant, harboring acquired resistance genes to multiple antibiotic classes, and chromosomal mutations conferring fluoroquinolone resistance. Three isolates additionally carried chromosomal insertions of the blaCTX-M-55 gene. Resistance to cefiderocol was observed in one isolate and was associated with CirA and Fiu truncation. Conclusions: These findings highlight ongoing dissemination of mcr-1.1-positive E. coli isolates in Tunisia, primarily driven by plasmid transfer. Continuous genomic surveillance and One Health-oriented antibiotic stewardship are essential to limit the spread of colistin-resistance and the emergence of resistance to newer agents such as cefiderocol.

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BibTeX
@article{jaidane2026reduced,
  title = {{Reduced susceptibility to cefiderocol among clinical MCR-1-producing Escherichia coli isolates from Tunisia}},
  author = {Nadia Jaidane and Thierry Naas and Souad Fayad and Pierre Châtre and Wejdene Mansour and Aymen Bouaziz and Pauline François and Laetitia Du Fraysseix and Bogdan I Iorga and Nahed A Al Laham and Lamia Tilouche and Farouk Barguellil and Marisa Haenni},
  journal = {Antibiotics},
  year = {2026},
  month = aug,
  doi = {10.3390/antibiotics15080802},
  url = {https://anses.hal.science/anses-05744052v1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Reduced susceptibility to cefiderocol among clinical MCR-1-producing Escherichia coli isolates from Tunisia
AU  - Nadia Jaidane
AU  - Thierry Naas
AU  - Souad Fayad
AU  - Pierre Châtre
AU  - Wejdene Mansour
AU  - Aymen Bouaziz
AU  - Pauline François
AU  - Laetitia Du Fraysseix
AU  - Bogdan I Iorga
AU  - Nahed A Al Laham
AU  - Lamia Tilouche
AU  - Farouk Barguellil
AU  - Marisa Haenni
PY  - 2026
DA  - 2026/08/18
JO  - Antibiotics
DO  - 10.3390/antibiotics15080802
UR  - https://anses.hal.science/anses-05744052v1
AB  - Background/Objectives: The emergence of plasmid-mediated mcr genes has enabled horizontal dissemination of resistance to colistin, a last-resort antibiotic against multidrug-resistant Enterobacterales. In Tunisia, genomic data on mcr-positive Escherichia coli are still limited. This study reports the genomic characterization of human clinical mcr-positive E. coli isolates from the Military Hospital of Tunis. Methods: Between August 2023 and March 2025, seven E. coli isolates with low-level colistin-resistance (MIC = 4–8 µg/mL) were collected from six patients. They were characterized by antibiotic susceptibility testing and WGS to determine resistome, MLST, genetic relatedness, and plasmid content. Results: The E. coli isolates belonged to diverse sequence types (STs), except for two isolates collected from the same patient 2.5 months apart, which were highly related. Overall, this pattern is consistent with a polyclonal spread. The mcr-1.1 gene was located on IncI2 (n = 5) or IncX4 (n = 2) plasmids, which exhibited high similarity both among themselves and in comparison with plasmids previously reported in human and livestock isolates. Most isolates were multidrug-resistant, harboring acquired resistance genes to multiple antibiotic classes, and chromosomal mutations conferring fluoroquinolone resistance. Three isolates additionally carried chromosomal insertions of the blaCTX-M-55 gene. Resistance to cefiderocol was observed in one isolate and was associated with CirA and Fiu truncation. Conclusions: These findings highlight ongoing dissemination of mcr-1.1-positive E. coli isolates in Tunisia, primarily driven by plasmid transfer. Continuous genomic surveillance and One Health-oriented antibiotic stewardship are essential to limit the spread of colistin-resistance and the emergence of resistance to newer agents such as cefiderocol.
SN  - 2079-6382
ER  -