Genomic characterization of 16S rRNA methyltransferase-producing Escherichia coli isolates from the Parisian area, France

Background: The resistance to all aminoglycosides (AGs) conferred by 16S rRNA methyltransferase enzymes (16S-RMTases) is a major public health concern. Objectives: To characterize the resistance genotype, its genetic environment and plasmid support, and the phylogenetic relatedness of 16S-RMTase-producing Escherichia coli from France. Methods: We screened 137 E. coli isolates resistant to all clinically relevant AGs from nine Parisian hospitals for 16S-RMTases. WGS was performed on clinical isolates with high-level AG resistance (MIC >= 256mg/L) and their transformants. Results: Thirty of the 137 AG-resistant E. coli produced 16S-RMTases: 11 ArmA, 18 RmtB and 1 RmtC. The 16S-RMTase producers were also resistant to third-generation cephalosporins (90% due to a bla(CTX-M) gene), co-trimoxazole, fluoroquinolones and carbapenems (bla(NDM) and bla(VIM) genes) in 97%, 83%, 70% and 10% of cases, respectively. Phylogenomic diversity was high in ArmA producers, with 10 different STs, but a similar genetic environment, with the Tn1548 transposon carried by a plasmid closely related to pCTX-M-3 in 6/11 isolates. Conversely, RmtB producers belonged to 12 STs, the most frequent being ST405 and ST complex (STc) 10 (four and four isolates, respectively). The rmtB gene was carried by IncF plasmids in 10 isolates and was found in different genetic environments. The rmtC gene was carried by the pNDM-US plasmid. Conclusions: ArmA and RmtB are the predominant 16S-RMTases in France, but their spread follows two different patterns: (i) dissemination of a conserved genetic support carrying armA in E. coli with high levels of genomic diversity; and (ii) various genetic environments surrounding rmtB in clonally related E. coli.