Abstract

Pathogenic microorganisms exploit host metabolism for sustained survival by rewiring its metabolic interactions. Therefore, several metabolic changes are induced in both pathogen and host cells in the course of infection. A systems-based approach to elucidate those changes includes the integrative use of genome-scale metabolic networks and molecular omics data, with the overall goal of better characterizing infection mechanisms for novel treatment strategies. This review focuses on novel aspects of metabolism-oriented systems-based investigation of pathogen-human interactions. The reviewed approaches are the generation of dual-omics data for the characterization of metabolic signatures of pathogen-host interactions, the reconstruction of pathogen-host integrated genome-scale metabolic networks, which has a high potential to be applied to pathogen-gut microbiota interactions, and the structure-based analysis of enzymes playing role in those interactions. The integrative use of those approaches will pave the way for the identification of novel biomarkers and drug targets for the prediction and prevention of infectious diseases.

Highlights

  • One major focus of systems biology in medical research is the integrated use of high-throughput omics data and molecular interaction networks, with the overall goal of elucidating molecular mechanisms of diseases to identify potential biomarkers and personalized treatment strategies

  • Rather than investigating host and pathogen metabolisms separately, novel systems biology based approaches consider the pathogen-host interaction (PHI) system as a whole to elucidate the mechanisms of infection

  • The first integrated genome-scale metabolic network of pathogen-host interactions was reported for the Plasmodium falciparum infection in erythrocytes, where infection-specific gene expression data of the parasite was incorporated into flux prediction algorithm (Huthmacher et al, 2010)

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Summary

Introduction

One major focus of systems biology in medical research is the integrated use of high-throughput omics data and molecular interaction networks, with the overall goal of elucidating molecular mechanisms of diseases to identify potential biomarkers and personalized treatment strategies. This included collecting transcriptomic, proteomic, or metabolomic data from pathogens or infected hosts on one side, and developing interaction models focusing on the enzymes and reactions of crucial metabolic pathways on the other side (Bumann, 2009). The generation of dual-omics data makes it possible to extend the genome-scale metabolic network modeling of pathogens to PHI systems, by simultaneously considering pathogen and host metabolisms.

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