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EMBO reports 4, 7, 692–698 (2003)
doi:10.1038/sj.embor.embor881
AOP Published online: 6 June 2003
Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of anthrax and Gram-positive pathogens
James R. Brown1, Daniel Gentry2, Julie A. Becker1, Karen Ingraham2, David J. Holmes2 & Michael J. Stanhope1
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1 Bioinformatics Division, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, Collegeville, Pennsylvania 19426, USA
2 Microbial Genetics Department, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, Collegeville, Pennsylvania 19426, USA
To whom correspondence should be addressed
James R. Brown Tel: +1 610 917 6374; Fax: +1 610 917 7901; james.r.brown@gsk.com
Michael J. Stanhope Tel: +1 610 917 6577; Fax: +1 610 917 7901; michael.j.stanhope@gsk.com
Received 10 March 2003; Accepted 13 May 2003; Published online 6 June 2003.
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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.
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