Difference between revisions of "PMID:24391520"
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| + | !align=left align='left' bgcolor='#CCCCFF' |Citation | ||
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| + | '''Paradis-Bleau, C, Kritikos, G, Orlova, K, Typas, A and Bernhardt, TG''' (2014) A genome-wide screen for bacterial envelope biogenesis mutants identifies a novel factor involved in cell wall precursor metabolism. ''PLoS Genet.'' '''10''':e1004056 | ||
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| + | !align=left align='left' bgcolor='#CCCCFF' |Abstract | ||
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| + | The cell envelope of Gram-negative bacteria is a formidable barrier that is difficult for antimicrobial drugs to penetrate. Thus, the list of treatments effective against these organisms is small and with the rise of new resistance mechanisms is shrinking rapidly. New therapies to treat Gram-negative bacterial infections are therefore sorely needed. This goal will be greatly aided by a detailed mechanistic understanding of envelope assembly. Although excellent progress in the identification of essential envelope biogenesis systems has been made in recent years, many aspects of the process remain to be elucidated. We therefore developed a simple, quantitative, and high-throughput assay for mutants with envelope biogenesis defects and used it to screen an ordered single-gene deletion library of Escherichia coli. The screen was robust and correctly identified numerous mutants known to be involved in envelope assembly. Importantly, the screen also implicated 102 genes of unknown function as encoding factors that likely impact envelope biogenesis. As a proof of principle, one of these factors, ElyC (YcbC), was characterized further and shown to play a critical role in the metabolism of the essential lipid carrier used for the biogenesis of cell wall and other bacterial surface polysaccharides. Further analysis of the function of ElyC and other hits identified in our screen is likely to uncover a wealth of new information about the biogenesis of the Gram-negative envelope and the vulnerabilities in the system suitable for drug targeting. Moreover, the screening assay described here should be readily adaptable to other organisms to study the biogenesis of different envelope architectures. | ||
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| + | !align=left align='left' bgcolor='#CCCCFF' |Links | ||
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| + | [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=24391520 PubMed] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879167 PMC3879167] | ||
| + | Online version:[http://dx.doi.org/10.1371/journal.pgen.1004056 10.1371/journal.pgen.1004056] | ||
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| + | !align=left align='left' bgcolor='#CCCCFF' |Keywords | ||
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| + | Cell Membrane/genetics; Cell Membrane/metabolism; Cell Membrane/ultrastructure; Cell Wall/genetics; Cell Wall/metabolism; Cell Wall/ultrastructure; Escherichia coli/genetics; Escherichia coli/growth & development; Genome, Bacterial; Mutation; Polysaccharides, Bacterial/genetics; Polysaccharides, Bacterial/metabolism | ||
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| + | ==Main Points of the Paper == | ||
| + | {{LitSignificance}} | ||
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| + | == Materials and Methods Used == | ||
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| + | ==Phenotype Annotations== | ||
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| + | ==Notes== | ||
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| + | ==References== | ||
| + | {{RefHelp}} | ||
| + | <references/> | ||
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| + | [[Category:Publication]] | ||
Latest revision as of 12:16, 21 June 2017
| Citation |
Paradis-Bleau, C, Kritikos, G, Orlova, K, Typas, A and Bernhardt, TG (2014) A genome-wide screen for bacterial envelope biogenesis mutants identifies a novel factor involved in cell wall precursor metabolism. PLoS Genet. 10:e1004056 |
|---|---|
| Abstract |
The cell envelope of Gram-negative bacteria is a formidable barrier that is difficult for antimicrobial drugs to penetrate. Thus, the list of treatments effective against these organisms is small and with the rise of new resistance mechanisms is shrinking rapidly. New therapies to treat Gram-negative bacterial infections are therefore sorely needed. This goal will be greatly aided by a detailed mechanistic understanding of envelope assembly. Although excellent progress in the identification of essential envelope biogenesis systems has been made in recent years, many aspects of the process remain to be elucidated. We therefore developed a simple, quantitative, and high-throughput assay for mutants with envelope biogenesis defects and used it to screen an ordered single-gene deletion library of Escherichia coli. The screen was robust and correctly identified numerous mutants known to be involved in envelope assembly. Importantly, the screen also implicated 102 genes of unknown function as encoding factors that likely impact envelope biogenesis. As a proof of principle, one of these factors, ElyC (YcbC), was characterized further and shown to play a critical role in the metabolism of the essential lipid carrier used for the biogenesis of cell wall and other bacterial surface polysaccharides. Further analysis of the function of ElyC and other hits identified in our screen is likely to uncover a wealth of new information about the biogenesis of the Gram-negative envelope and the vulnerabilities in the system suitable for drug targeting. Moreover, the screening assay described here should be readily adaptable to other organisms to study the biogenesis of different envelope architectures. |
| Links |
PubMed PMC3879167 Online version:10.1371/journal.pgen.1004056 |
| Keywords |
Cell Membrane/genetics; Cell Membrane/metabolism; Cell Membrane/ultrastructure; Cell Wall/genetics; Cell Wall/metabolism; Cell Wall/ultrastructure; Escherichia coli/genetics; Escherichia coli/growth & development; Genome, Bacterial; Mutation; Polysaccharides, Bacterial/genetics; Polysaccharides, Bacterial/metabolism |
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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<protect>
| Phenotype of | Taxon Information | Genotype Information (if known) | Condition Information | OMP ID | OMP Term Name | ECO ID | ECO Term Name | Notes | Status |
|---|---|---|---|---|---|---|---|---|---|
</protect>
Notes
References
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