Abstract
Drug resistance is a major healthcare challenge, resulting in a continuous need to develop new inhibitors. The development of these inhibitors requires an understanding of the mechanisms of resistance for a critical mass of occurrences. Recent genome editing technologies based on high-throughput DNA synthesis and sequencing may help to predict mutations resulting in resistance by testing large mutagenesis libraries. Here we describe the rationale of this approach, with examples and relevance to drug development and resistance in malaria.
Keywords:
DXR; drug resistance; fosmidomycin; genome editing; sequence to activity mapping.
MeSH terms
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Aldose-Ketose Isomerases / antagonists & inhibitors
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Aldose-Ketose Isomerases / chemistry*
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Aldose-Ketose Isomerases / metabolism
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Anti-Bacterial Agents / pharmacology
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Directed Molecular Evolution / methods*
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Drug Resistance / genetics*
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Fosfomycin / analogs & derivatives
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Fosfomycin / pharmacology
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Gene Library
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Malaria / drug therapy*
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Mutagenesis*
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Mutation
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Plasmodium falciparum / genetics
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Plasmodium falciparum / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
Substances
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Anti-Bacterial Agents
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Fosfomycin
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fosmidomycin
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1-deoxy-D-xylulose 5-phosphate reductoisomerase
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Aldose-Ketose Isomerases