IS26 mediated blaCTX-M-65 amplification in Escherichia coli increase the antibiotic resistance to cephalosporin in vivo.
J Glob Antimicrob Resist
; 35: 202-209, 2023 12.
Article
em En
| MEDLINE
| ID: mdl-37802302
ABSTRACT
OBJECTIVES:
To characterize two Escherichia coli strains isolated from a patient pre- and post-treatment, using ß-lactams and ß-lactam/ß-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 ß-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Cefalosporinas
/
Escherichia coli
Limite:
Humans
Idioma:
En
Revista:
J Glob Antimicrob Resist
Ano de publicação:
2023
Tipo de documento:
Article