IS26 mediated blaCTX-M-65 amplification in Escherichia coli increase the antibiotic resistance to cephalosporin in vivo

Autor: Yinping Wang, Jintao He, Long Sun, Yan Jiang, Lihua Hu, Sebastian Leptihn, Pengfei Zhu, Xiaoting Fu, Yunsong Yu, Xiaoting Hua
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Global Antimicrobial Resistance, Vol 35, Iss , Pp 202-209 (2023)
Druh dokumentu: article
ISSN: 2213-7165
DOI: 10.1016/j.jgar.2023.09.018
Popis: ABSTRACT: Objectives: To characterize two Escherichia coli strains isolated from a patient pre- and post-treatment, using β-lactams and β-lactam/β-lactamase inhibitor combinations (BLBLIs). Methods: A combination of antibiotic susceptibility testing (AST) with whole genome sequencing using Illumina and Oxford Nanopore platforms. Long-read sequencing and reverse transcription-quantitative PCR were performed to determine the copy numbers and expression levels of antibiotic resistance genes (ARGs), respectively. Effect on fitness costs were assessed by growth rate determination. Results: The strain obtained from the patient after the antibiotic treatment (XH989) exhibited higher resistance to cefepime, BLBLIs and quinolones compared with the pre-treatment strain (XH987). Sequencing revealed IS26-mediated duplications of a IS26-fosA3-blaCTX-M-65 plasmid-embedded element in strain XH989. Long-read sequencing (7.4 G data volume) indicated a variation in copy numbers of blaCTX-M-65 within one single culture of strain XH989. Increased copy numbers of the IS26-fosA3-blaCTX-M-65 element were correlated with higher CTX-M-65 expression level and did not impose fitness costs, while facilitating faster growth under high antibiotic concentrations. Conclusion: Our study is an example from the clinic how BLBLIs and β-lactams exposure in vivo possibly promoted the amplification of an IS26-multiple drug resistance (MDR) region. The observation of a copy number variation seen with the blaCTX-M-65 gene in the plasmid of the post-treatment strain expands our knowledge of insertion sequence dynamics and evolution during treatment.
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