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Combining Shigella Tn-seq data with Gold-standard E. coli Gene Deletion Data Suggests Rare Transitions between Essential and Non-essential Gene Functionality

Nikki E. Freed, Dirk Bumann, Olin K. Silander
doi: https://doi.org/10.1101/038869
Nikki E. Freed
1Institute of Natural and Mathematical Sciences, Massey University, Auckland, New Zealand
2Infection Biology, Biozentrum, University of Basel, Basel, Switzerland
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Dirk Bumann
2Infection Biology, Biozentrum, University of Basel, Basel, Switzerland
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Olin K. Silander
1Institute of Natural and Mathematical Sciences, Massey University, Auckland, New Zealand
3Computational and Systems Biology, Biozentrum, University of Basel, Basel, Switzerland
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  • For correspondence: olinsilander@gmail.com
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Abstract

Gene essentiality - whether or not a gene is necessary for cell growth - is a fundamental component of gene function. It is not well established how quickly gene essentiality can change, as few studies have compared empirical measures of essentiality between closely related organisms. Here we present the results of a Tn-seq experiment designed to detect essential protein coding genes in the bacterial pathogen Shigella flexneri 2a 2457T on a genome-wide scale. Superficial analysis of this data suggested that 451 protein-coding genes in this Shigella strain are critical for robust cellular growth on rich media. Comparison of this set of genes with a gold-standard data set of essential genes in the closely related Escherichia coli K12 BW25113 suggested that an excessive number of genes appeared essential in Shigella but non-essential in E. coli. Importantly, and in converse to this comparison, we found no genes that were essential in E. coli and non-essential in Shigella, suggesting that many genes were artefactually inferred as essential in Shigella. Controlling for such artefacts resulted in a much smaller set of discrepant genes. Among these, we identified three sets of functionally related genes; two of which have previously been implicated as critical for Shigella growth, but which are dispensable for E. coli growth. The data presented here highlight the small number of protein coding genes for which we have strong evidence that their essentiality status differs between the closely related bacterial taxa E. coli and Shigella. A set of genes involved in acetate utilization provides a canonical example. These results leave open the possibility of developing strain-specific antibiotic treatments targeting such differentially essential genes, but suggest that such opportunities may be rare in closely related bacteria.

Author Summary Essential genes are those that encode proteins required for growth and survival in a particular environment. We performed experiments using transposons, genetic elements that disrupt gene function, to determine the set of essential genes in the pathogenic bacteria Shigella flexneri. We then compared our results to the well-characterized set of essential genes in the closely related, yet non-pathogenic, bacteria Escherichia coli. We found only a small number of genes that are important for growth in Shigella flexneri, yet not in Escherichia coli. We believe these findings are interesting for several reasons; they help us better understand how quickly the functions of proteins change over time; they suggest possible targets for developing strain-specific antibiotic treatments; and they expand our basic understanding of this pathogen’s metabolic processes.

  • List of abbreviations used

    bp
    base pairs
    Shigella – Shigella flexneri
    2a 2457T
    E. coli – Escherichia coli
    BW25113
    ORF
    open reading frame
    PEC
    Profiling the E coli Chromosome database
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    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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    Posted February 09, 2016.
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    Combining Shigella Tn-seq data with Gold-standard E. coli Gene Deletion Data Suggests Rare Transitions between Essential and Non-essential Gene Functionality
    Nikki E. Freed, Dirk Bumann, Olin K. Silander
    bioRxiv 038869; doi: https://doi.org/10.1101/038869
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    Combining Shigella Tn-seq data with Gold-standard E. coli Gene Deletion Data Suggests Rare Transitions between Essential and Non-essential Gene Functionality
    Nikki E. Freed, Dirk Bumann, Olin K. Silander
    bioRxiv 038869; doi: https://doi.org/10.1101/038869

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