A module located at a chromosomal integration hot spot is responsible for the multidrug resistance of a reference
Mathilde Lescat1, Alexandra Calteau, Claire Hoede
1INSERM U722 and Université Paris 7 Denis Diderot, Site Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France.
Abstract:
Escherichia coli clonal group A (CGA) commonly exhibits a distinctive multidrug antimicrobial resistance phenotype-i.e., resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, tetracycline, and trimethoprim (ACSSuTTp)-and has accounted for up to 50% of trimethoprim-sulfamethoxazole-resistant E. coli urinary tract infections in some locales. Annotation of the whole-genome sequencing of UMN026, a reference CGA strain, clarified the genetic basis for this strain's ACSSuTTp antimicrobial resistance phenotype. Most of the responsible genes were clustered in a unique 23-kbp chromosomal region, designated the genomic resistance module (GRM), which occurred within a 105-kbp genomic island situated at the leuX tRNA. The GRM is characterized by numerous remnants of mobilization and rearrangement events suggesting multiple horizontal transfers. Additionally, comparative genomic analysis of the leuX tRNA genomic island in 14 sequenced E. coli genomes showed that this region is a hot spot of integration, with the presence/absence of specific subregions being uncorrelated with either the phylogenetic group or the pathotype. Our data illustrate the importance of whole-genome sequencing in the detection of genetic elements involved in antimicrobial resistance. Additionally, this is the first documentation of the bla(TEM) and dhfrVII genes in a chromosomal location in E. coli strains.
Insights
Escherichia coli clonal group A (CGA) strains often show multidrug resistance. Whole-genome sequencing identified a specific genomic region, the GRM, responsible for this resistance in CGA E. coli.
Area of Science:
- Microbiology
- Genomics
- Antimicrobial Resistance
Background:
- Escherichia coli clonal group A (CGA) is frequently associated with multidrug resistance, including resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, tetracycline, and trimethoprim (ACSSuTTp).
- This resistance pattern contributes significantly to trimethoprim-sulfamethoxazole-resistant E. coli urinary tract infections.
Purpose of the Study:
- To elucidate the genetic basis of the ACSSuTTp multidrug resistance phenotype in the reference CGA strain UMN026.
- To characterize the genomic region responsible for antimicrobial resistance in CGA E. coli.
Main Methods:
- Whole-genome sequencing and annotation of the UMN026 E. coli strain.
- Comparative genomic analysis of the leuX tRNA genomic island across 14 sequenced E. coli genomes.
Main Results:
- A unique 23-kbp chromosomal region, termed the genomic resistance module (GRM), was identified within a 105-kbp genomic island at the leuX tRNA.
- The GRM contains genes conferring the ACSSuTTp resistance phenotype and shows evidence of multiple horizontal gene transfers.
- The leuX tRNA genomic island is a hot spot for integration, with variable subregions not correlating with phylogenetic group or pathotype.
Conclusions:
- Whole-genome sequencing is crucial for identifying genetic elements driving antimicrobial resistance.
- This study provides the first evidence of bla(TEM) and dhfrVII genes located on the chromosome in E. coli strains.
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