RT Journal Article
T1 Comparative Metabolomics between Mycobacterium tuberculosis and the MTBVAC Vaccine Candidate.
A1 Díaz, Caridad
A1 Pérez Del Palacio, José
A1 Valero-Guillén, Pedro Luis
A1 Mena García, Patricia
A1 Pérez, Irene
A1 Vicente, Francisca
A1 Martín, Carlos
A1 Genilloud, Olga
A1 Sánchez Pozo, Antonio
A1 Gonzalo-Asensio, Jesús
K1 live attenuated vaccine
K1 phoP
K1 phosphatidylinositol mannosides
K1 vaccination biomarkers
K1 virulence
AB 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.
YR 2019
FD 2019-05-30
LK http://hdl.handle.net/10668/13975
UL http://hdl.handle.net/10668/13975
LA en
DS RISalud
RD Apr 10, 2025