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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 blaCTX-M-243.
- Source :
- Journal of Antimicrobial Chemotherapy (JAC); Feb2022, Vol. 77 Issue 2, p381-390, 10p
- Publication Year :
- 2022
-
Abstract
- <bold>Background: </bold>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.<bold>Objectives: </bold>To characterize a novel blaCTX-M variant harboured by a multidrug-resistant Escherichia coli isolate of sequence type ST354.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]
- Subjects :
- GENETIC variation
CHROMOSOME duplication
DNA copy number variations
SINGLE molecules
GENES
DRUG resistance in bacteria
NUCLEOTIDE sequencing
ESCHERICHIA coli
RESEARCH
GENETIC mutation
RESEARCH methodology
EVALUATION research
HYDROLASES
ENTEROBACTERIACEAE
COMPARATIVE studies
ESCHERICHIA coli diseases
RESEARCH funding
ANTIBIOTICS
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 03057453
- Volume :
- 77
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Journal of Antimicrobial Chemotherapy (JAC)
- Publication Type :
- Academic Journal
- Accession number :
- 155028649
- Full Text :
- https://doi.org/10.1093/jac/dkab407