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dc.contributor.authorParadis-Bleau, Catherineen_US
dc.contributor.authorKritikos, Georgeen_US
dc.contributor.authorOrlova, Katyaen_US
dc.contributor.authorTypas, Athanasiosen_US
dc.contributor.authorBernhardt, Thomas G.en_US
dc.date.accessioned2014-03-11T13:26:27Z
dc.date.issued2014en_US
dc.identifier.citationParadis-Bleau, Catherine, George Kritikos, Katya Orlova, Athanasios Typas, and Thomas G. Bernhardt. 2014. “A Genome-Wide Screen for Bacterial Envelope Biogenesis Mutants Identifies a Novel Factor Involved in Cell Wall Precursor Metabolism.” PLoS Genetics 10 (1): e1004056. doi:10.1371/journal.pgen.1004056. http://dx.doi.org/10.1371/journal.pgen.1004056.en
dc.identifier.issn1553-7390en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879568
dc.description.abstractThe 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.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pgen.1004056en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879167/pdf/en
dash.licenseLAAen_US
dc.subjectBiologyen
dc.subjectGeneticsen
dc.subjectGenomicsen
dc.subjectMicrobiologyen
dc.subjectMolecular Cell Biologyen
dc.subjectSystems Biologyen
dc.titleA Genome-Wide Screen for Bacterial Envelope Biogenesis Mutants Identifies a Novel Factor Involved in Cell Wall Precursor Metabolismen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Geneticsen
dash.depositing.authorBernhardt, Thomas G.en_US
dc.date.available2014-03-11T13:26:27Z
dc.identifier.doi10.1371/journal.pgen.1004056*
dash.contributor.affiliatedBernhardt, Thomas


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