The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung
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 stu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.763364/full |
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| author | Mariateresa Coppola Rachel P-J. Lai Rachel P-J. Lai Robert J. Wilkinson Robert J. Wilkinson Robert J. Wilkinson Tom H. M. Ottenhoff |
| author_facet | Mariateresa Coppola Rachel P-J. Lai Rachel P-J. Lai Robert J. Wilkinson Robert J. Wilkinson Robert J. Wilkinson Tom H. M. Ottenhoff |
| author_sort | Mariateresa Coppola |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T14:10:26Z |
| format | Article |
| id | doaj.art-76ba31ced65644ab960217e2702e2944 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T14:10:26Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-76ba31ced65644ab960217e2702e29442022-12-21T19:38:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-12-011210.3389/fimmu.2021.763364763364The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the LungMariateresa Coppola0Rachel P-J. Lai1Rachel P-J. Lai2Robert J. Wilkinson3Robert J. Wilkinson4Robert J. Wilkinson5Tom H. M. Ottenhoff6Department Infectious Diseases, Leiden University Medical Center (LUMC), Leiden, Netherlands The Francis Crick Institute, London, United KingdomDepartment of Infectious Diseases, Imperial College London, London, United Kingdom The Francis Crick Institute, London, United KingdomDepartment of Infectious Diseases, Imperial College London, London, United KingdomDepartment of Medicine, Institute of Infectious Disease and Molecular Medicine, Wellcome Centre for Infectious Diseases Research in Africa, Cape Town, South AfricaDepartment Infectious Diseases, Leiden University Medical Center (LUMC), Leiden, NetherlandsMycobacterium 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.763364/fullMycobacterium tuberculosis (MTB)transcriptomictuberculosisvaccinetherapyantigen discovery |
| spellingShingle | Mariateresa Coppola Rachel P-J. Lai Rachel P-J. Lai Robert J. Wilkinson Robert J. Wilkinson Robert J. Wilkinson Tom H. M. Ottenhoff The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung Frontiers in Immunology Mycobacterium tuberculosis (MTB) transcriptomic tuberculosis vaccine therapy antigen discovery |
| title | The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung |
| title_full | The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung |
| title_fullStr | The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung |
| title_full_unstemmed | The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung |
| title_short | The In Vivo Transcriptomic Blueprint of Mycobacterium tuberculosis in the Lung |
| title_sort | in vivo transcriptomic blueprint of mycobacterium tuberculosis in the lung |
| topic | Mycobacterium tuberculosis (MTB) transcriptomic tuberculosis vaccine therapy antigen discovery |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.763364/full |
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