Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of anthrax and Gram-positive pathogens

EMBO Rep. 2003 Jul;4(7):692-8. doi: 10.1038/sj.embor.embor881.


The screening of new antibiotics against several bacterial strains often reveals unexpected occurrences of natural drug resistance. Two examples of this involve specific inhibitors of Staphylococcus aureus isoleucyl-transfer-RNA synthetase 1 (IleRS1) and, more recently, Streptococcus pneumoniae methionyl-tRNA synthetase 1 (MetRS1). In both cases, resistance is due to the presence of a second gene that encodes another synthetase (IleRS2 or MetRS2). Here, we show that both S. pneumoniae MetRS2 and S. aureus IleRS2 have closely related homologues in the Gram-positive bacterium Bacillus anthracis, the causative agent of anthrax. Furthermore, similar to drug-resistant pathogens, strains of B. anthracis and its closest relative, B. cereus, also have wild-type ileS1 and metS1 genes. Clostridium perfringens, the causative agent of gangrene, also has two metS genes, whereas Oceanobacillus iheyensis isolated from deep-sea sediments has a single ileS2-type gene. This study shows the importance of understanding complex evolutionary networks of ancient horizontal gene transfer for the development of novel antibiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anthrax / microbiology
  • Bacillus anthracis / enzymology
  • Bacillus anthracis / genetics*
  • Computational Biology
  • Drug Resistance, Bacterial / genetics*
  • Evolution, Molecular
  • Gene Transfer, Horizontal / genetics*
  • Gram-Positive Bacteria / enzymology*
  • Gram-Positive Bacteria / genetics*
  • Isoleucine-tRNA Ligase / chemistry
  • Isoleucine-tRNA Ligase / genetics*
  • Methionine-tRNA Ligase / chemistry
  • Methionine-tRNA Ligase / genetics*
  • Molecular Sequence Data
  • Phylogeny
  • Sequence Homology, Amino Acid


  • Methionine-tRNA Ligase
  • Isoleucine-tRNA Ligase

Associated data

  • GENBANK/AY280849
  • GENBANK/AY280850
  • GENBANK/AY280851
  • GENBANK/AY280852
  • GENBANK/AY280853
  • GENBANK/AY280854
  • GENBANK/AY280855
  • GENBANK/AY282419
  • GENBANK/AY282420
  • GENBANK/AY282421
  • GENBANK/AY282422
  • GENBANK/AY282423
  • GENBANK/AY282424
  • GENBANK/AY282425
  • GENBANK/AY282426
  • GENBANK/AY282427
  • GENBANK/AY282428
  • GENBANK/AY282429
  • GENBANK/AY282430
  • GENBANK/AY282431
  • GENBANK/AY282432
  • GENBANK/AY282433
  • GENBANK/AY282434
  • GENBANK/AY282435
  • GENBANK/AY282436