Exploiting genomics to discover new antibiotics

被引:82
作者
McDevitt, D [1 ]
Rosenberg, M [1 ]
机构
[1] GlaxoSmithKline, Antimicrobials & Host Def CEDD, Collegeville, PA 19426 USA
关键词
D O I
10.1016/S0966-842X(01)02235-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
There is an urgent need to develop new classes of antibiotics to tackle the increase in resistance in many common bacterial pathogens. One strategy to develop new antibiotics is to identify and exploit new molecular targets and this strategy is being driven by the wealth of new genome sequence information now available. Additionally, new technologies have been developed to validate new antibacterial targets, for example, new technologies have been developed to enable rapid determination of whether a gene is essential and to assess the transcription status of a putative target during infection. As a result, many novel validated targets have now been identified and for some, appropriate high-throughput screens against diverse compound collections have been carried out. Novel antibiotic leads are emerging from these genomics-derived targeted screens and the challenge now is to optimize and develop these leads to become part of the next generation of antibiotics.
引用
收藏
页码:611 / 617
页数:7
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共 60 条
  • [1] Bacterial virulence as a target for antimicrobial chemotherapy
    Alksne, LE
    Projan, SJ
    [J]. CURRENT OPINION IN BIOTECHNOLOGY, 2000, 11 (06) : 625 - 636
  • [2] Identification and analysis of bacterial protein secretion inhibitors utilizing a SecA-LacZ reporter fusion system
    Alksne, LE
    Burgio, P
    Hu, W
    Feld, B
    Singh, MP
    Tuckman, M
    Petersen, PJ
    Labthavikul, P
    McGlynn, M
    Barbieri, L
    McDonald, L
    Bradford, P
    Dushin, RG
    Rothstein, D
    Projan, SJ
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2000, 44 (06) : 1418 - 1427
  • [3] Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
    Altschul, SF
    Madden, TL
    Schaffer, AA
    Zhang, JH
    Zhang, Z
    Miller, W
    Lipman, DJ
    [J]. NUCLEIC ACIDS RESEARCH, 1997, 25 (17) : 3389 - 3402
  • [4] Amber D, 2000, SCIENTIST, V14, P1
  • [5] Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents
    Apfel, C
    Banner, DW
    Bur, D
    Dietz, M
    Hirata, T
    Hubschwerlen, C
    Locher, H
    Page, MGP
    Pirson, W
    Rossé, G
    Specklin, JL
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (12) : 2324 - 2331
  • [6] Peptide deformylase as an antibacterial drug target:: Target validation and resistance development
    Apfel, CM
    Locher, H
    Evers, S
    Takács, B
    Hubschwerlen, C
    Pirson, W
    Page, MGP
    Keck, W
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (04) : 1058 - 1064
  • [7] Aravind L., 2000, GENOME BIOL, V1, DOI DOI 10.1186/GB-2000-1-4-RESEARCH0007
  • [8] Staphylococcus aureus:: A well-armed pathogen
    Archer, GL
    [J]. CLINICAL INFECTIOUS DISEASES, 1998, 26 (05) : 1179 - 1181
  • [9] A genome-based approach for the identification of essential bacterial genes
    Arigoni, F
    Talabot, F
    Peitsch, M
    Edgerton, MD
    Meldrum, E
    Allet, E
    Fish, R
    Jamotte, T
    Curchod, ML
    Loferer, H
    [J]. NATURE BIOTECHNOLOGY, 1998, 16 (09) : 851 - 856
  • [10] Antibacterial agents that inhibit two-component signal transduction systems
    Barrett, JF
    Goldschmidt, RM
    Lawrence, LE
    Foleno, B
    Chen, R
    Demers, JP
    Johnson, S
    Kanojia, R
    Fernandez, J
    Bernstein, J
    Licata, L
    Donetz, A
    Huang, S
    Hlasta, DJ
    Macielag, MJ
    Ohemeng, K
    Frechette, R
    Frosco, MB
    Klaubert, DH
    Whiteley, JM
    Wang, L
    Hoch, JA
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (09) : 5317 - 5322