WarA, a remote homolog of NpmA and KamB from Nocardia wallacei, confers broad spectrum aminoglycoside resistance in Nocardia and Mycobacteria

Yizhak Hershko, Ella Rannon, Amos Adler, David Burstein, Daniel Barkan

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Aminoglycoside resistance in bacteria is typically conferred by specific drug-modifying enzymes. Infrequently, such resistance is achieved through 16S ribosomal RNA methyltransferases, such as NpmA and KamB encoded by Escherichia coli and Streptoalloteichus tenebrarius, respectively. These enzymes are not widespread and have not been described in Nocardia species to date. Methods: We report the genomic mining of 18 Nocardia wallacei isolates that were found to be specifically and substantially resistant to amikacin. Results: We identified a gene coding for a protein with very distant homology to NpmA and KamB. However, 3-D modeling revealed that the tertiary structure of these three proteins was highly similar. Cloning and expressing this gene in two susceptible bacteria Nocardia asteroides, and Mycobacterium smegmatis (another Actinobacterium) led to high-level, pan-aminoglycoside resistance in both cases. We named this gene warA (Wallacei Amikacin Resistance A). Conclusions: This is the first description and experimental characterization of a gene of this family in Nocardia, and the first demonstration that such activity could lead to pan-aminoglycoside resistance in Mycobacteria as well. The discovery of this novel gene has important biotechnology and clinical implications.

Original languageEnglish
Article number107089
JournalInternational Journal of Antimicrobial Agents
Volume63
Issue number2
DOIs
StatePublished - Feb 2024
Externally publishedYes

Keywords

  • 16S rRNA methylation
  • Amikacin
  • Aminoglycoside
  • Antimicrobial resistance
  • Mycobacteria
  • Nocardia

Fingerprint

Dive into the research topics of 'WarA, a remote homolog of NpmA and KamB from Nocardia wallacei, confers broad spectrum aminoglycoside resistance in Nocardia and Mycobacteria'. Together they form a unique fingerprint.

Cite this