title: Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of anthrax and Gram-positive pathogens.
abstract: 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.
authors.affiliation: Bioinformatics Division, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, Collegeville, Pennsylvania 19426, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Brown
authors.forename: Daniel
authors.initials: D
authors.lastname: Gentry
authors.forename: Julie A
authors.initials: JA
authors.lastname: Becker
authors.forename: Karen
authors.initials: K
authors.lastname: Ingraham
authors.forename: David J
authors.initials: DJ
authors.lastname: Holmes
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Stanhope
mesh_terms: D000595:Amino Acid Sequence; D000881:Anthrax / Q000382:microbiology; D001408:Bacillus anthracis / Q000201:enzymology / Q000235:genetics*; D019295:Computational Biology; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal / Q000235:genetics*; D006094:Gram-Positive Bacteria / Q000201:enzymology* / Q000235:genetics*; D007533:Isoleucine-tRNA Ligase / Q000737:chemistry / Q000235:genetics*; D008718:Methionine-tRNA Ligase / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D008718:Methionine-tRNA Ligase; D007533:Isoleucine-tRNA Ligase