Comparative Metabolomics between Mycobacterium tuberculosis and the MTBVAC Vaccine Candidate.
ACS Infect Dis
; 5(8): 1317-1326, 2019 08 09.
Article
em En
| MEDLINE
| ID: mdl-31099236
ABSTRACT
MTBVAC is a live attenuated M. tuberculosis vaccine constructed by genetic deletions in the phoP and fadD26 virulence genes. The MTBVAC vaccine is currently in phase 2 clinical trials with newborns and adults in South Africa, one of the countries with the highest incidence. Although MTBVAC has been extensively characterized by genomics, transcriptomics, lipidomics, and proteomics, its metabolomic profile is yet unknown. Accordingly, in this study we aim to identify differential metabolites between M. tuberculosis and MTBVAC. To this end, an untargeted metabolomics approach based on liquid chromatography coupled to high-resolution mass spectrometry was implemented in order to explore the main metabolic differences between M. tuberculosis and MTBVAC. As an outcome, we identified a set of 34 metabolites involved in diverse bacterial biosynthetic pathways. A consistent increase in the phosphatidylinositol species was observed in the vaccine candidate relative to its parental strain. This phenotype resulted in an increased production of phosphatidylinositol mannosides, a novel PhoP-regulated phenotype in the most widespread lineages of M. tuberculosis. This study represents a step ahead in our understanding of the MTBVAC vaccine, and some of the differential metabolites identified in this work might be used as potential vaccination biomarkers.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Vacinas contra a Tuberculose
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Vias Biossintéticas
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Metabolômica
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Mycobacterium tuberculosis
Idioma:
En
Revista:
ACS Infect Dis
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Espanha