A Novel Tryptophanyl-tRNA Synthetase Gene Confers High-Level Resistance to Indolmycin

被引:23
作者
Vecchione, James J. [1 ]
Sello, Jason K. [1 ]
机构
[1] Brown Univ, Dept Chem, Providence, RI 02912 USA
关键词
MICROORGANISM STREPTOMYCES-AVERMITILIS; MUPIROCIN PSEUDOMONIC ACID; COMPLETE GENOME SEQUENCE; ANTIBIOTIC-RESISTANCE; COELICOLOR A3(2); INHIBITORS; AGENT; BIOSYNTHESIS; FLUORESCENS;
D O I
10.1128/AAC.00723-09
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:3972 / 3980
页数:9
相关论文
共 39 条
[1]   Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2) [J].
Bentley, SD ;
Chater, KF ;
Cerdeño-Tárraga, AM ;
Challis, GL ;
Thomson, NR ;
James, KD ;
Harris, DE ;
Quail, MA ;
Kieser, H ;
Harper, D ;
Bateman, A ;
Brown, S ;
Chandra, G ;
Chen, CW ;
Collins, M ;
Cronin, A ;
Fraser, A ;
Goble, A ;
Hidalgo, J ;
Hornsby, T ;
Howarth, S ;
Huang, CH ;
Kieser, T ;
Larke, L ;
Murphy, L ;
Oliver, K ;
O'Neil, S ;
Rabbinowitsch, E ;
Rajandream, MA ;
Rutherford, K ;
Rutter, S ;
Seeger, K ;
Saunders, D ;
Sharp, S ;
Squares, R ;
Squares, S ;
Taylor, K ;
Warren, T ;
Wietzorrek, A ;
Woodward, J ;
Barrell, BG ;
Parkhill, J ;
Hopwood, DA .
NATURE, 2002, 417 (6885) :141-147
[2]   Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of anthrax and Gram-positive pathogens [J].
Brown, JR ;
Gentry, D ;
Becker, JA ;
Ingraham, K ;
Holmes, DJ ;
Stanhope, MJ .
EMBO REPORTS, 2003, 4 (07) :692-698
[3]   The antimicrobial natural product chuangxinmycin and some synthetic analogues are potent and selective inhibitors of bacterial tryptophanyl tRNA synthetase [J].
Brown, MJ ;
Carter, PS ;
Fenwick, AE ;
Fosberry, AP ;
Hamprecht, DW ;
Hibbs, MJ ;
Jarvest, RL ;
Mensah, L ;
Milner, PH ;
O'Hanlon, PJ ;
Pope, AJ ;
Richardson, CM ;
West, A ;
Witty, DR .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (21) :3171-3174
[4]   MUPIROCIN (PSEUDOMONIC ACID) - A PROMISING NEW TOPICAL ANTIMICROBIAL AGENT [J].
CASEWELL, MW ;
HILL, RLR .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1987, 19 (01) :1-5
[5]   Sampling the antibiotic resistome [J].
D'Costa, VM ;
McGrann, KM ;
Hughes, DW ;
Wright, GD .
SCIENCE, 2006, 311 (5759) :374-377
[6]   Resistance redux - Infectious diseases, antibiotic resistance and the future of mankind [J].
Davies, Julian .
EMBO REPORTS, 2008, 9 (Suppl 1) :S18-S21
[7]   Characterization of the mupirocin biosynthesis gene cluster from Pseudomonas fluorescens NCIMB 10586 [J].
El-Sayed, AK ;
Hothersall, J ;
Cooper, SM ;
Stephens, E ;
Simpson, TJ ;
Thomas, CM .
CHEMISTRY & BIOLOGY, 2003, 10 (05) :419-430
[8]   PSEUDOMONIC ACID - ANTIBIOTIC PRODUCED BY PSEUDOMONAS-FLUORESCENS [J].
FULLER, AT ;
MELLOWS, G ;
WOOLFORD, M ;
BANKS, GT ;
BARROW, KD ;
CHAIN, EB .
NATURE, 1971, 234 (5329) :416-&
[9]   Variable sensitivity to bacterial methionyl-tRNA synthetase inhibitors reveals subpopulations of Streptococcus pneumoniae with two distinct methionyl-tRNA synthetase genes [J].
Gentry, DR ;
Ingraham, KA ;
Stanhope, MJ ;
Rittenhouse, S ;
Jarvest, RL ;
O'Hanlon, PJ ;
Brown, JR ;
Holmes, DJ .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (06) :1784-1789
[10]   Integration site for streptomyces phage φBT1 and development of site-specific integrating vectors [J].
Gregory, MA ;
Till, R ;
Smith, MCM .
JOURNAL OF BACTERIOLOGY, 2003, 185 (17) :5320-5323