Difference between revisions of "PMID:20674514"

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'''Becket, E, Chen, F, Tamae, C and Miller, JH'''  (2010) Determination of hypersensitivity to genotoxic agents among Escherichia coli single gene knockout mutants.''DNA Repair (Amst.)'' '''9''':949-57
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We have tested the KEIO collection of 3985 different viable single gene knockouts in Escherichia coli to identify genes whose loss increases sensitivity to one or more of six different chemotherapeutic agents and mutagens: Bleomycin (BLM), Cisplatin (CPT), ICR-191 (ICR), 5-azacytidine (5AZ), Zebularine (ZEB), and 5-bromo-2'-deoxyuridine (5BdU). We discovered a set of 156 strains that display a significant increase in sensitivity to at least one of the agents tested. Each genotoxic agent generates a distinct "sensitivity profile" that is characteristic of the agent. Comparison with an independent study of sensitivity profiles for an extensive set of antibiotics pinpoints those effects that are relatively specific for each agent. In some cases engineered double mutants have greatly increased effects. These results provide insight into the mechanism of action of each agent, and define targets for the design of co-drugs that can potentiate these agents. An example is the finding that mutants lacking one of several genes in the folate biosynthetic pathway are hypersensitive to ZEB, leading to a demonstration of synergy between trimethoprim and ZEB.
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[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=20674514 PubMed]
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Online version:[http://dx.doi.org/10.1016/j.dnarep.2010.06.008 10.1016/j.dnarep.2010.06.008]
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Escherichia coli; Gene Knockout Techniques; Microbial Sensitivity Tests; Mutagens; Mutation
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==Main Points of the Paper ==
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== Materials and Methods Used ==
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==Phenotype Annotations==
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==Notes==
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==References==
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[[Category:Publication]]

Latest revision as of 08:04, 29 March 2012

Citation

Becket, E, Chen, F, Tamae, C and Miller, JH (2010) Determination of hypersensitivity to genotoxic agents among Escherichia coli single gene knockout mutants.DNA Repair (Amst.) 9:949-57

Abstract

We have tested the KEIO collection of 3985 different viable single gene knockouts in Escherichia coli to identify genes whose loss increases sensitivity to one or more of six different chemotherapeutic agents and mutagens: Bleomycin (BLM), Cisplatin (CPT), ICR-191 (ICR), 5-azacytidine (5AZ), Zebularine (ZEB), and 5-bromo-2'-deoxyuridine (5BdU). We discovered a set of 156 strains that display a significant increase in sensitivity to at least one of the agents tested. Each genotoxic agent generates a distinct "sensitivity profile" that is characteristic of the agent. Comparison with an independent study of sensitivity profiles for an extensive set of antibiotics pinpoints those effects that are relatively specific for each agent. In some cases engineered double mutants have greatly increased effects. These results provide insight into the mechanism of action of each agent, and define targets for the design of co-drugs that can potentiate these agents. An example is the finding that mutants lacking one of several genes in the folate biosynthetic pathway are hypersensitive to ZEB, leading to a demonstration of synergy between trimethoprim and ZEB.

Links

PubMed Online version:10.1016/j.dnarep.2010.06.008

Keywords

Escherichia coli; Gene Knockout Techniques; Microbial Sensitivity Tests; Mutagens; Mutation

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Main Points of the Paper

Please summarize the main points of the paper.

Materials and Methods Used

Please list the materials and methods used in this paper (strains, plasmids, antibodies, etc).

Phenotype Annotations

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Phenotype of Taxon Information Genotype Information (if known) Condition Information OMP ID OMP Term Name ECO ID ECO Term Name Notes Status
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Notes

References

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