Integrative genome-scale metabolic analysis of Vibrio vulnificus for drug targeting and discovery

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Title
Integrative genome-scale metabolic analysis of Vibrio vulnificus for drug targeting and discovery
Author(s)
H U Kim; S Y Kim; Haeyoung Jeong; T Y Kim; J J Kim; H E Choy; K Y Yi; J H Rhee; S Y Lee
Bibliographic Citation
Molecular Systems Biology, vol. 7, pp. 460-460
Publication Year
2011
Abstract
Although the genomes of many microbial pathogens have been studied to help identify effective drug targets and novel drugs, such efforts have not yet reached full fruition. In this study, we report a systems biological approach that efficiently utilizes genomic information for drug targeting and discovery, and apply this approach to the opportunistic pathogen Vibrio vulnificus CMCP6. First, we partially re-sequenced and fully re-annotated the V. vulnificus CMCP6 genome, and accordingly reconstructed its genome-scale metabolic network, VvuMBEL943. The validated network model was employed to systematically predict drug targets using the concept of metabolite essentiality, along with additional filtering criteria. Target genes encoding enzymes that interact with the five essential metabolites finally selected were experimentally validated. These five essential metabolites are critical to the survival of the cell, and hence were used to guide the cost-effective selection of chemical analogs, which were then screened for antimicrobial activity in a whole-cell assay. This approach is expected to help fill the existing gap between genomics and drug discovery.
Keyword
drug discoverydrug targetinggenome analysismetabolic networkVibrio vulnificus
ISSN
1744-4292
Publisher
Wiley
DOI
http://dx.doi.org/10.1038/msb.2010.115
Type
Article
Appears in Collections:
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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