Ultra-deep long-read sequencing detects IS-mediated gene duplications as a potential trigger to generate arrays of resistance genes and a mechanism to induce novel gene variants such as bla CTX-M-243
2021 | journal article. A publication with affiliation to the University of Göttingen.
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Ultra-deep long-read sequencing detects IS-mediated gene duplications as a potential trigger to generate arrays of resistance genes and a mechanism to induce novel gene variants such as bla CTX-M-243
Schuster, C. F.; Weber, R. E.; Weig, M.; Werner, G. & Pfeifer, Y. (2021)
Journal of Antimicrobial Chemotherapy, 77(2) pp. 381-390. DOI: https://doi.org/10.1093/jac/dkab407
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- Authors
- Schuster, Christopher F.; Weber, Robert E.; Weig, Michael; Werner, Guido; Pfeifer, Yvonne
- Abstract
- Abstract Background Extended-spectrum β-lactamases (ESBLs) are enzymes that can render their hosts resistant to various β-lactam antibiotics. CTX-M-type enzymes are the most prevalent ESBLs and the main cause of resistance to third-generation cephalosporins in Enterobacteriaceae. The number of described CTX-M types is continuously rising, currently comprising over 240 variants. During routine screening we identified a novel blaCTX-M gene. Objectives To characterize a novel blaCTX-M variant harboured by a multidrug-resistant Escherichia coli isolate of sequence type ST354. Methods Antibiotic susceptibilities were determined using broth microdilution. Genome and plasmid sequences were reconstructed using short- and long-read sequencing. The novel blaCTX-M locus was analysed using long-read and Sanger sequencing. Plasmid polymorphisms were determined in silico on a single plasmid molecule level. Results The novel blaCTX-M-243 allele was discovered alongside a nearly identical blaCTX-M-104-containing gene array on a 219 kbp IncHI2A plasmid. CTX-M-243 differed from CTX-M-104 by only one amino acid substitution (N109S). Ultra-deep (2300-fold coverage) long-read sequencing revealed dynamic scaling of the blaCTX-M genetic contexts from one to five copies. Further antibiotic resistance genes such as blaTEM-1 also exhibited sequence heterogeneity but were stable in copy number. Conclusions We identified the novel ESBL gene blaCTX-M-243 and illustrate a dynamic system of varying blaCTX-M copy numbers. Our results highlight the constant emergence of new CTX-M family enzymes and demonstrate a potential evolutionary platform to generate novel ESBL variants and possibly other antibiotic resistance genes.
- Issue Date
- 2021
- Journal
- Journal of Antimicrobial Chemotherapy
- ISSN
- 0305-7453
- eISSN
- 1460-2091
- Language
- English