TY - JOUR
T1 - The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung
AU - Coppola, Mariateresa
AU - Lai, Rachel P.J.
AU - Wilkinson, Robert J.
AU - Ottenhoff, Tom H.M.
N1 - Funding Information: EC HORIZON2020 TBVAC2020, Grant Agreement No. 643381 (MC, TO); EC ITN FP7 VACTRAIN project (MC, TO); NWO-TOP project Grant Agreement No. 91214038 (TO). Francis Crick Institute funded by URI grant FC0010218, Cancer Research UK (FC0010218) and Wellcome (FC0010218) (RP-JL, RW); Wellcome grant 104803 (RW); Wellcome grant 203135 (RW). Publisher Copyright: Copyright © 2021 Coppola, Lai, Wilkinson and Ottenhoff.
PY - 2021/12/22
Y1 - 2021/12/22
N2 - Mycobacterium tuberculosis (Mtb) genes encoding proteins targeted by vaccines and drugs should be expressed in the lung, the main organ affected by Mtb, for these to be effective. However, the pulmonary expression of most Mtb genes and their proteins remains poorly characterized. The aim of this study is to fill this knowledge gap. We analyzed large scale transcriptomic datasets from specimens of Mtb-infected humans, TB-hypersusceptible (C3H/FeJ) and TB-resistant (C57BL/6J) mice and compared data to in vitro cultured Mtb gene-expression profiles. Results revealed high concordance in the most abundantly in vivo expressed genes between pulmonary Mtb transcriptomes from different datasets and different species. As expected, this contrasted with a lower correlation found with the highest expressed Mtb genes from in vitro datasets. Among the most consistently and highly in vivo expressed genes, 35 have not yet been explored as targets for vaccination or treatment. More than half of these genes are involved in protein synthesis or metabolic pathways. This first lung-oriented multi-study analysis of the in vivo expressed Mtb-transcriptome provides essential data that considerably increase our understanding of pulmonary TB infection biology, and identifies novel molecules for target-based TB-vaccine and drug development.
AB - Mycobacterium tuberculosis (Mtb) genes encoding proteins targeted by vaccines and drugs should be expressed in the lung, the main organ affected by Mtb, for these to be effective. However, the pulmonary expression of most Mtb genes and their proteins remains poorly characterized. The aim of this study is to fill this knowledge gap. We analyzed large scale transcriptomic datasets from specimens of Mtb-infected humans, TB-hypersusceptible (C3H/FeJ) and TB-resistant (C57BL/6J) mice and compared data to in vitro cultured Mtb gene-expression profiles. Results revealed high concordance in the most abundantly in vivo expressed genes between pulmonary Mtb transcriptomes from different datasets and different species. As expected, this contrasted with a lower correlation found with the highest expressed Mtb genes from in vitro datasets. Among the most consistently and highly in vivo expressed genes, 35 have not yet been explored as targets for vaccination or treatment. More than half of these genes are involved in protein synthesis or metabolic pathways. This first lung-oriented multi-study analysis of the in vivo expressed Mtb-transcriptome provides essential data that considerably increase our understanding of pulmonary TB infection biology, and identifies novel molecules for target-based TB-vaccine and drug development.
KW - Mycobacterium tuberculosis (MTB)
KW - antigen discovery
KW - therapy
KW - transcriptomic
KW - tuberculosis
KW - vaccine
UR - http://www.scopus.com/inward/record.url?scp=85122242201&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2021.763364
DO - https://doi.org/10.3389/fimmu.2021.763364
M3 - Article
C2 - 35003075
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 763364
ER -