Association of the novel aminoglycoside resistance determinant RmtF with NDM carbapenemase in enterobacteriaceae isolated in India and the UK

Laura Hidalgo, Katie L. Hopkins, Belen Gutierrez, Cristina M. Ovejero, Suruchi Shukla, Stephen Douthwaite, Kashi N. Prasad, Neil Woodford, Bruno Gonzalez-Zorn*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    74 Citations (Scopus)

    Abstract

    Objectives: 16S rRNA methyltransferases are an emerging mechanism conferring high-level resistance to clinically relevant aminoglycosides and have been associated with important mechanisms such as NDM-1. We sought genes encoding these enzymes in isolates highly resistant (MIC > 200 mg/L) to gentamicin and amikacin from an Indian hospital and we additionally screened for the novel RmtF enzyme in 132 UK isolates containing NDM. Methods: All highly aminoglycoside-resistant isolates were screened for armA and rmtA-E by PCR, with cloning experiments performed for isolates negative for these genes. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was used to determine the methylation target of the novel RmtF methyltransferase. RmtF-bearing strains were characterized further, including susceptibility testing, PFGE, electroporation, PCR-based replicon typing and multilocus sequence typing of rmtF-bearing plasmids. Results: High-level aminoglycoside resistance was detected in 140/1000 (14%) consecutive isolates of Enterobacteriaceae from India. ArmA, RmtB and RmtC were identified among 46%, 20% and 27% of these isolates, respectively. The novel rmtF gene was detected in 34 aminoglycoside-resistant isolates (overall prevalence 3.4%), most (59%) of which also possessed a blaNDM gene; rmtF was detected in 6 NDM producers from the UK. It was found on different plasmid backbones. Four and two isolates showed resistance to tigecycline and colistin, respectively. Conclusions: RmtF was often found in association with NDM in members of the Enterobacteriaceae and on diverse plasmids. It is of clinical concern that the RmtF- and NDM-positive strains identified here show additional resistance to tigecycline and colistin, current drugs of last resort for the treatment of serious bacterial infections.

    Original languageEnglish
    Pages (from-to)1543-1550
    Number of pages8
    JournalJournal of Antimicrobial Chemotherapy
    Volume68
    Issue number7
    DOIs
    Publication statusPublished - 1 Jul 2013

    Keywords

    • 16S rRNA methyltransferases
    • Resistance
    • antimicrobial

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