Genomics and antimicrobial drug discovery

Each potential new antibiotic must meet a number of criteria before it is approved for use, and the choice of an appropriate target is the first step in this process. It is helpful to review the utility of genomic information with regard to some of the key criteria which antimicrobial targets must m...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 1999-03, Vol.43 (3), p.439-446
Main Authors: MOIR, D. T, SHAW, K. J, HARE, R. S, VOVIS, G. F
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents
Anti-Bacterial Agents - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacteria
Bacteria - drug effects
Bacteria - genetics
Base Sequence
Biological and medical sciences
Databases, Factual
DNA, Bacterial - genetics
Genome, Bacterial
Medical sciences
Minireview
Minireviews
Pharmacology. Drug treatments
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Summary:Each potential new antibiotic must meet a number of criteria before it is approved for use, and the choice of an appropriate target is the first step in this process. It is helpful to review the utility of genomic information with regard to some of the key criteria which antimicrobial targets must meet. In general, (i) a target should provide adequate selectivity and spectrum, yielding a drug which is specific or highly selective against the microbe with respect to the human host but also active against the desired spectrum of pathogens; (ii) a target should be essential for growth or viability of the pathogen, at least essential under conditions of infection; and (iii) something about the function of the target should be known so that assays and high-throughput screens can be built. Identification of potential new targets can proceed from any one of these criteria, but ultimately all must be met by a successful target. For example, a variety of methods may be used to find genes which are essential for the survival of an organism under defined conditions or which are necessary for infectivity in an animal model. Comparative genomics may be used to identify potential targets which are shared across multiple microbial species. Several tools, primarily sequence similarity based, may be used to predict the function of most genes so that specific pathways can be targeted. As discussed below, genomic sequence information provides assistance in all of these areas: selectivity, spectrum, functionality, and essentiality.
ISSN:0066-4804
1098-6596
DOI:10.1128/aac.43.3.439