Combining Tn-seq with comparative genomics identifies proteins uniquely essential in Shigella flexneri

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dc.contributor.authorFreed NE
dc.contributor.authorBumann D
dc.contributor.authorSilander O
dc.coverage.spatialQueenstown, New Zealand
dc.date.available3/09/2015
dc.date.finish-date4/09/2015
dc.date.issued3/09/2015
dc.date.start-date3/09/2015
dc.description.abstractProtein functions that are essential for the growth of bacterial pathogens provide promising targets for antibacterial treatment. This is especially true if those functions are uniquely essential for the pathogen, as this might allow the development of targeted antibiotics, i.e. those that disrupt essential functions only for the pathogenic bacteria. Here we present the results of a Tn-seq experiment designed to detect essential protein coding genes in Shigella flexneri 2a 2457T on a genome-wide scale. Our results suggest that 471 protein-coding genes in this organism are critical for cellular growth in rich media. Comparing this set of essential genes (the essential gene complement) with their orthologues in the closely related organism Escherichia coli K12 BW25113 revealed a significant number of genes that are essential in Shigella but not in E. coli, suggesting that the functional correspondence of these proteins had changed. Notably, we also identified a set of functionally related genes that are essential in Shigella but which have no orthologues in E. coli. We found an extreme bias in proteins that have evolved to provide essential functions, with many proteins essential in Shigella but not E. coli, but with none (or very few) being essential in E. coli but not Shigella. We also identify a set- of genes involved in nucleotide biosynthesis that are essential in Shigella, but which lack orthologues in E. coli. Consequently, the data presented here suggest that the essential gene complement can quickly become organism specific, especially for pathogenic organisms whose genomes might have reduced robustness in their metabolic capacity (e.g. functional redundancy), or a reduced numbers of protein coding genes. These results thus open the possibility of developing antibiotic treatments that target differentially essential genes, which may exist even between very closely related strains of bacteria.
dc.identifier.citation2015
dc.identifier.elements-id256340
dc.identifier.harvestedMassey_Dark
dc.identifier.urihttps://hdl.handle.net/10179/7510
dc.sourceQueenstown Research Week Computational Genomics
dc.titleCombining Tn-seq with comparative genomics identifies proteins uniquely essential in Shigella flexneri
dc.typeconference
pubs.notesNot known
pubs.organisational-group/Massey University
pubs.organisational-group/Massey University/College of Sciences
pubs.organisational-group/Massey University/College of Sciences/School of Natural and Computational Sciences
pubs.organisational-group/Massey University/College of Sciences/School of Natural Sciences
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