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Genome-wide assessment of Mycobacterium tuberculosis conditionally essential metabolic pathways

View ORCID ProfileYusuke Minato, View ORCID ProfileDaryl M Gohl, Joshua M Thiede, Jeremy Matthew Chacón, View ORCID ProfileWilliam R Harcombe, View ORCID ProfileFumito Maruyama, View ORCID ProfileAnthony D Baughn
doi: https://doi.org/10.1101/534289
Yusuke Minato
University of Minnesota Medical School;
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  • For correspondence: yminato@umn.edu
Daryl M Gohl
University of Minnesota Genomics Center;
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  • For correspondence: dmgohl@umn.edu
Joshua M Thiede
University of Minnesota;
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  • For correspondence: thied022@umn.edu
Jeremy Matthew Chacón
University of Minnesota;
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  • For correspondence: chaco001@umn.edu
William R Harcombe
University of Minnesota;
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Fumito Maruyama
Kyoto University
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  • For correspondence: maruyama.fumito.5e@kyoto-u.ac.jp
Anthony D Baughn
University of Minnesota;
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  • For correspondence: abaughn@umn.edu
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Abstract

Better understanding of essential cellular functions in pathogenic bacteria is important for the development of more effective antimicrobial agents. We performed a comprehensive identification of essential genes in Mycobacterium tuberculosis, the major causative agent of tuberculosis, using a combination of transposon insertion sequencing (Tn-seq) and comparative genomic analysis. To identify conditional essential genes by Tn-seq, we used media with different nutrient composition. Although many conditional gene essentialities were affected by the presence of relevant nutrient sources, we also found that the essentiality of genes in a subset of metabolic pathways was unaffected by metabolites. Comparative genomic analysis revealed that not all essential genes identified by Tn-seq were fully conserved within the M. tuberculosis complex including some existing anti-tubercular drug target genes. In addition, we utilized an available M. tuberculosis genome-scale metabolic model, iSM810, to predict M. tuberculosis gene essentiality in silico. Comparing the sets of essential genes experimentally identified by Tn-seq to those predicted in silico reveals the capabilities and limitations of gene essentiality predictions highlighting the complexity of M. tuberculosis essential metabolic functions. This study provides a promising platform to study essential cellular functions in M. tuberculosis.

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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 4.0 International license.
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Posted January 29, 2019.
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Genome-wide assessment of Mycobacterium tuberculosis conditionally essential metabolic pathways
Yusuke Minato, Daryl M Gohl, Joshua M Thiede, Jeremy Matthew Chacón, William R Harcombe, Fumito Maruyama, Anthony D Baughn
bioRxiv 534289; doi: https://doi.org/10.1101/534289
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Genome-wide assessment of Mycobacterium tuberculosis conditionally essential metabolic pathways
Yusuke Minato, Daryl M Gohl, Joshua M Thiede, Jeremy Matthew Chacón, William R Harcombe, Fumito Maruyama, Anthony D Baughn
bioRxiv 534289; doi: https://doi.org/10.1101/534289

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