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An updated genome-scale metabolic network reconstruction of Pseudomonas aeruginosa PA14 to characterize mucin-driven shifts in bacterial metabolism.

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.

SUBMITTER: Payne DD

PROVIDER: S-EPMC8501023 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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An updated genome-scale metabolic network reconstruction of Pseudomonas aeruginosa PA14 to characterize mucin-driven shifts in bacterial metabolism.

Payne Dawson D DD Renz Alina A Dunphy Laura J LJ Lewis Taylor T Dräger Andreas A Papin Jason A JA

NPJ systems biology and applications 20211008 1

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 cur ...[more]

PMID: 34625561

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Project description:Extracellular electron transfer (EET), the reduction of compounds that shuttle electrons to distal oxidants, can support bacterial survival when preferred oxidants are not directly accessible. EET has been shown to contribute to virulence in some pathogenic organisms and is required for current generation in mediator-based fuel cells. In several species, components of the electron transport chain (ETC) have been implicated in electron shuttle reduction, raising the question of how shuttling-based metabolism is integrated with primary routes of metabolic electron flow. The clinically relevant bacterium Pseudomonas aeruginosa can utilize carbon sources (i.e., electron donors) covering a broad range of reducing potentials and possesses a branched ETC that can be modulated to optimize respiratory efficiency. It also produces electron shuttles called phenazines that facilitate intracellular redox balancing, increasing the complexity of its metabolic potential. In this study, we investigated the reciprocal influence of respiratory metabolism and phenazine-associated physiology in P. aeruginosa PA14. We found that phenazine production affects respiratory activity and terminal oxidase gene expression and that carbon source identity influences the mechanisms enabling phenazine reduction. Furthermore, we found that growth in biofilms, a condition for which phenazine metabolism is critical to normal development and redox balancing, affects the composition of the P. aeruginosa phenazine pool. Together, these findings can aid interpretation of P. aeruginosa behavior during host infection and provide inroads to understanding the cross talk between primary metabolism and shuttling-based physiology in the diverse bacteria that carry out EET.IMPORTANCE The clinically relevant pathogen Pseudomonas aeruginosa uses diverse organic compounds as electron donors and possesses multiple enzymes that transfer electrons from central metabolism to O2 These pathways support a balanced intracellular redox state and produce cellular energy. P. aeruginosa also reduces secondary metabolites called phenazines to promote redox homeostasis and virulence. In this study, we examined the reciprocal relationship between these primary and secondary routes of electron flow. We found that phenazines affect respiratory function and that the complement of phenazines produced is strongly affected by growth in assemblages called biofilms. These results provide a more nuanced understanding of P. aeruginosa redox metabolism and may inform strategies for treating persistent infections caused by this bacterium.

Dataset Information

An updated genome-scale metabolic network reconstruction of Pseudomonas aeruginosa PA14 to characterize mucin-driven shifts in bacterial metabolism.

Publications

An updated genome-scale metabolic network reconstruction of Pseudomonas aeruginosa PA14 to characterize mucin-driven shifts in bacterial metabolism.

Similar Datasets

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