Harnessing the power of the genome in the search for new antibiotics

被引:132
作者
Rosamond, L [1 ]
Allsop, A [1 ]
机构
[1] AstraZeneca, Macclesfield SK10 4TG, Cheshire, England
关键词
D O I
10.1126/science.287.5460.1973
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Over the past 40 years, the search for new antibiotics has been Largely restricted to well-known compound classes active against a standard set of drug targets. Although many effective compounds have been discovered, insufficient chemical variability has been generated to prevent a serious escalation in clinical resistance. Recent advances in genomics have provided an opportunity to expand the range of potential drug targets and have facilitated a fundamental shift from direct antimicrobial screening programs toward rational target-based strategies. The application of genome-based technologies such as expression profiling and proteomics will Lead to further changes in the drug discovery paradigm by combining the strengths and advantages of both screening strategies in a single program.
引用
收藏
页码:1973 / 1976
页数:4
相关论文
共 35 条
  • [11] A reporter gene assay for fungal sterol biosynthesis inhibitors
    Dixon, G
    Scanlon, D
    Cooper, S
    Broad, P
    [J]. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1997, 62 (2-3) : 165 - 171
  • [12] The yeast genome project: What did we learn?
    Dujon, B
    [J]. TRENDS IN GENETICS, 1996, 12 (07) : 263 - 270
  • [13] Protein interaction maps for complete genomes based on gene fusion events
    Enright, AJ
    Iliopoulos, I
    Kyrpides, NC
    Ouzounis, CA
    [J]. NATURE, 1999, 402 (6757) : 86 - 90
  • [14] Overview of resistance in the 1990s
    File, TM
    [J]. CHEST, 1999, 115 (03) : 3S - 8S
  • [15] Drug therapy - Antimicrobial-drug resistance
    Gold, HS
    Moellering, RC
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (19) : 1445 - 1453
  • [16] GRAY CP, 1998, EXPERT OPIN INVEST D, V7, P147
  • [17] Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors
    Gray, NS
    Wodicka, L
    Thunnissen, AMWH
    Norman, TC
    Kwon, SJ
    Espinoza, FH
    Morgan, DO
    Barnes, G
    LeClerc, S
    Meijer, L
    Kim, SH
    Lockhart, DJ
    Schultz, PG
    [J]. SCIENCE, 1998, 281 (5376) : 533 - 538
  • [18] HAWKEY PM, 1998, BRIT MED J, V317
  • [19] Dissecting the biology of a pathogen during infection
    Heithoff, DM
    Conner, CP
    Mahan, MJ
    [J]. TRENDS IN MICROBIOLOGY, 1997, 5 (12) : 509 - 513
  • [20] ILLINGWORTH R, UNPUB