An Updated Genome-Scale Metabolic Network Reconstruction of Pseudomonas Aeruginosa PA14 to Characterize Mucin-Driven Shifts in Bacterial Metabolism

Author: ORCID icon orcid.org/0000-0001-5392-8492
Payne, Dawson, Biomedical Engineering - School of Engineering and Applied Science, University of Virginia
Advisor:
Papin, Jason, MD-BIOM Biomedical Eng, University of Virginia
Abstract:

Mucins are present in mucosal membranes throughout the body and play a key role in the microbe clearance and infection prevention. Understanding the metabolic responses of pathogens to mucins will further enable the development of protective approaches against infections. We update the genome-scale metabolic network reconstruction (GENRE) of one such pathogen, Pseudomonas aeruginosa PA14, through metabolic coverage expansion, format update, extensive annotation addition, and literature-based curation to produce iPau21. We then validate iPau21 through MEMOTE, growth rate, carbon source utilization, and gene essentiality testing to demonstrate its improved quality and predictive capabilities. We then integrate the GENRE with transcriptomic data in order to generate context-specific models of P. aeruginosa metabolism. The contextualized models recapitulated known phenotypes of unaltered growth and a differential utilization of fumarate metabolism, while also revealing an increased utilization of propionate metabolism upon MUC5B exposure. This work serves to validate iPau21 and demonstrate its utility for providing biological insights.

Degree:
MS (Master of Science)
Keywords:
metabolism, genome-scale metabolic model, pseudomonas aeruginosa, mucin
Related Links:
  • github.com/dawsonpayne/iPau21
  • identifiers.org/biomodels.db/MODEL2106110001
  • https://www.nature.com/articles/s41540-021-00198-2
  • Language:
    English
    Rights:
    All rights reserved (no additional license for public reuse)
    Issued Date:
    2021/11/05