Resumen de Development and application of multiplatform metabolomic pipelines for the study of infectious diseases
INTRODUCTION: Pathogens are exogenous biological agents capable of infecting a host organism, potentially causing disease. Upon establishment of the infectious disease, both the pathogen and host metabolism experience substantial alterations, as a result of the establishment of host-pathogen interactions. Alterations in the concentration of metabolites can be studied in a holistic manner by mass spectrometry-based metabolomics.
MATERIALS AND METHODS: In the present chapter-based thesis, a comprehensive review of infectious disease metabolomics is presented, followed by the application and development of multiplatform metabolomic pipelines that combine liquid chromatography coupled to mass-spectrometry (LC/MS), gas chromatography coupled to mass spectrometry (GC/MS) and capillary electrophoresis coupled to mass-spectrometry (CE/MS). These approaches were applied to study mice lung tissue following Mycobacterium tuberculosis infection, Leishmania donovani-infected human macrophages, Babesia divergens-infected erythrocytes and Haemophilus influenzae cultures. Metabolite alterations were associated to functional processes triggered by M. tuberculosis, L. donovani and B. divergens infection.
RESULTS AND DISCUSSION: Overall, the performance of multiplatform mass spectrometry-based metabolomic studies in the samples described above allowed us to explain from a metabolism perspective the pathogenesis of M. tuberculosis, L. donovani and B. divergens. Additionally, the endometabolome of H. influenzae was characterized.
CONCLUSIONS The studies performed in the present thesis allowed us to generate panels of altered metabolites in samples not analyzed previously by mass spectrometry-based metabolomics. These metabolites were related with functional processes that could partly explain the pathogenesis of M. tuberculosis, L. donovani and B. divergens. The results obtained herein could serve as a foundation for future validation studies.
