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Physiological niche informs evolution of metabolic function and corresponding drug targets of pathobionts

View ORCID ProfileEmma M. Glass, Lillian R. Dillard, Andrew S. Warren, Jason A. Papin
doi: https://doi.org/10.1101/2022.11.10.515998
Emma M. Glass
1Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
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Lillian R. Dillard
2Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA
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Andrew S. Warren
3Biocomplexity Institute and Initiative, University of Virginia, Charlottesville, Virginia, USA
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Jason A. Papin
1Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
2Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA
4Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA
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  • For correspondence: papin@virginia.edu
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ABSTRACT

Pathogens pose a major risk to human health globally, causing 44% of deaths in low-resource countries. Currently, there are over 500 known bacterial pathobionts, covering a wide range of functional capabilities. Some well-known pathobionts are well characterized computationally and experimentally. However, to gain a deeper understanding of how pathobionts are evolutionarily related to the principles that govern their different functions and ultimately identify possible targeted antimicrobials, we must consider both well-known and lesser-known pathobionts. Here, we developed a database of genome-scale metabolic network reconstructions (GENREs) called PATHGENN, which contains 914 models of pathobiont metabolism to address these questions related to functional metabolic evolution and adaptation. We determined the metabolic phenotypes across all known pathobionts and the role of isolate environment in functional metabolic adaptation. We also predicted novel antimicrobial targets for bacteria specific to their physiological niche. Understanding the functional metabolic similarities between pathobionts is the first step to ultimately developing a precision medicine framework for addressing all infections.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
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 November 13, 2022.
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Physiological niche informs evolution of metabolic function and corresponding drug targets of pathobionts
Emma M. Glass, Lillian R. Dillard, Andrew S. Warren, Jason A. Papin
bioRxiv 2022.11.10.515998; doi: https://doi.org/10.1101/2022.11.10.515998
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Physiological niche informs evolution of metabolic function and corresponding drug targets of pathobionts
Emma M. Glass, Lillian R. Dillard, Andrew S. Warren, Jason A. Papin
bioRxiv 2022.11.10.515998; doi: https://doi.org/10.1101/2022.11.10.515998

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