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Antimicrobial Agents and Chemotherapy, September 2009, p. 3972-3980, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00723-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Novel Tryptophanyl-tRNA Synthetase Gene Confers High-Level Resistance to Indolmycin{triangledown} ,{dagger}

James J. Vecchione and Jason K. Sello*

Department of Chemistry, Brown University, 324 Brook Street, Providence, Rhode Island 02912

Received 28 May 2009/ Accepted 12 June 2009

Indolmycin, a potential antibacterial drug, competitively inhibits bacterial tryptophanyl-tRNA synthetases. An effort to identify indolmycin resistance genes led to the discovery of a gene encoding an indolmycin-resistant isoform of tryptophanyl-tRNA synthetase. Overexpression of this gene in an indolmycin-sensitive strain increased the indolmycin MIC 60-fold. Its transcription and distribution in various bacterial genera were assessed. The level of resistance conferred by this gene was compared to that of a known indolmycin resistance gene and to those of genes with resistance-conferring point mutations.

* Corresponding author. Mailing address: Department of Chemistry, Brown University, 324 Brook St., Providence, RI 02912. Phone: (401) 863-1194. Fax: (401) 863-9046. E-mail: Jason_Sello{at}Brown.edu

{triangledown} Published ahead of print on 22 June 2009.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

Antimicrobial Agents and Chemotherapy, September 2009, p. 3972-3980, Vol. 53, No. 9
0066-4804/09/$08.00+0     doi:10.1128/AAC.00723-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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