The sequencing of microbial genomes is revolutionizing the discovery of novel antifungal drugs, providing the tools for the rational identification of novel targets and compounds. High throughput genomic sequencing, combined with fragment assembly tools, has delivered a cornucopia of sequence information to assist in the search of new targets.
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Figure 17.20. mc-510,027.
Genomic information, combined with the ability to selectively delete or modify genes cf interest, is proving useful in evaluating the selectivity of a target and its essentiality for growth. In addition, comparative genomics allows the identification of potential targets shared across fungal species. For instance, entire biochemical pathways can be reconstructed and compared in different pathogens. Sequence comparisons may also provide some indication of potential mammalian toxicity if proteins of similar sequence exist in mammalian sequence databases.
Numerous databases. available over the Internet and easily downloaded onto local servers, are now available that contain both sequence and functionality information. In addition. certain commercial databases are available for nonexclusive use by commercial subscribers.
Overall, the genomic revolution is expected to have a profound impact on antifungal drug discovery, with the potential for the identification of new agents with novel mechanisms of action (183).
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