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Microb Genom. 2018 Mar;4(3). doi: 10.1099/mgen.0.000163. Epub 2018 Mar 20.

Comparative 'omics analyses differentiate Mycobacterium tuberculosis and Mycobacterium bovis and reveal distinct macrophage responses to infection with the human and bovine tubercle bacilli.

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1​UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
†​Present address: European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
2​Animal Genomics Laboratory, UCD School of Agriculture and Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
‡​Present address: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Headington, Oxford OX3 7FY, UK.
3​Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich CH-8093, Switzerland.
§​Present address: Department of Human Genetics, University of California, Los Angeles, USA.
¶​Present address: Quantitative Proteomics and Proteome Centre Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
4​Tuberculosis Diagnostics and Immunology Research Centre, UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
5​UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
6​UCD School of Medicine, University College Dublin, Dublin 4, Ireland.
7​UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin 4, Ireland.


Members of the Mycobacterium tuberculosis complex (MTBC) are the causative agents of tuberculosis in a range of mammals, including humans. A key feature of MTBC pathogens is their high degree of genetic identity yet distinct host tropism. Notably, while Mycobacterium bovis is highly virulent and pathogenic for cattle, the human pathogen M. tuberculosis is attenuated in cattle. Previous research also suggests that host preference amongst MTBC members has a basis in host innate immune responses. To explore MTBC host tropism, we present in-depth profiling of the MTBC reference strains M. bovis AF2122/97 and M. tuberculosis H37Rv at both the global transcriptional and the translational level via RNA-sequencing and SWATH MS. Furthermore, a bovine alveolar macrophage infection time course model was used to investigate the shared and divergent host transcriptomic response to infection with M. tuberculosis H37Rv or M. bovis AF2122/97. Significant differential expression of virulence-associated pathways between the two bacilli was revealed, including the ESX-1 secretion system. A divergent transcriptional response was observed between M. tuberculosis H37Rv and M. bovis AF2122/97 infection of bovine alveolar macrophages, in particular cytosolic DNA-sensing pathways at 48 h post-infection, and highlights a distinct engagement of M. bovis with the bovine innate immune system. The work presented here therefore provides a basis for the identification of host innate immune mechanisms subverted by virulent host-adapted mycobacteria to promote their survival during the early stages of infection.


Mycobacterium bovis; macrophage; proteomics; transcriptomics; tuberculosis

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