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Mycobacterium tuberculosis Mce1 protein complex initiates rapid induction of transcription of genes involved in substrate trafficking

Genes & Immunity volume 13, pages 496–502 (2012)Cite this article

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Abstract

The mammalian cell entry (Mce)1 protein complex has an important role during the initial phase of a Mycobacterium tuberculosis (M. tuberculosis) infection. Murine macrophages were infected with M. tuberculosis H37Rv or Δ-mce1 H37Rv, and total RNA was isolated from the host cells at 15, 30 and 60 min, and 4 and 10 h post-infection. With the aim of studying the role for the Mce1 protein complex on host gene expression, the RNA was hybridized onto 44 K whole-genome microarrays. Selected genes were verified by reverse-transcriptase quantitative PCR (RT-QPCR). ‘Transport’ was the most overrepresented biological process during the first hour post H37Rv infection. Five genes (Abca1 (21.0-fold), Slc16a10 (3.1-fold), Slc6a12 (17.9-fold), Slc6a8 (2.3-fold) and Nr1h3, (5.5-fold)) involved in substrate trafficking were verified by RT-QPCR to be upregulated by >2-fold 1 h post H37Rv infection. By 1 h post Δ-mce1 H37Rv infection, only Abca1 and Slc6a12 were upregulated by >2-fold. A number of other genes, which may be directly involved in substrate trafficking or share the same transcription, were found to have expression profiles similar to the genes involved in substrate trafficking. The Mce1 protein complex has a significant role in the transcriptional activation of genes involved in substrate trafficking during the initial phase of an M. tuberculosis infection.

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Acknowledgements

We thank Karl-Henning Kalland and Kari Rostad for constructive advice, Kristi Øvreås and Kjell Petersen for technical assistance, Haukeland University Hospital for P3-laboratory facilities, the Norwegian Microarray Consortium, Bergen, for microarray facilities, and the FUGE bioinformatics platform for valuable bioinformatics support. This study was funded by the Research Council of Norway project no. 179342 and 196362, and the Western Norway Regional Health Authority project no. 911207 and 911265.

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Author notes

  1. H Valvatne

    Present address: 8Current address: Intervet International B.V.,Wim de Körvestraat 35, PO Box 31 5830 AA Boxmeer, The Netherlands.,

  2. T M Doherty

    Present address: 9Current address: GlaxoSmithKline, Brøndby, Copenhagen, Denmark.,

Authors and Affiliations

  1. Department of Microbiology and Immunology, The Gade Institute, University of Bergen, Bergen, Norway

    R Stavrum, H Valvatne & H M S Grewal

  2. Department of Clinical Medicine, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

    A-K Stavrum

  3. Department of Informatics, University of Bergen, Bergen, Norway

    A-K Stavrum & I Jonassen

  4. Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, CA, USA

    L W Riley

  5. Department of Microbiology, Haukeland University Hospital, Bergen, Norway

    E Ulvestad & H M S Grewal

  6. Computational Biology Unit, Uni Computing, Uni Research AS, Bergen, Norway

    I Jonassen

  7. Department of Infectious Disease Immunology, Statens Serum Institute, Copenhagen, Denmark

    T M Doherty

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  1. R Stavrum
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Correspondence to R Stavrum.

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Stavrum, R., Valvatne, H., Stavrum, AK. et al. Mycobacterium tuberculosis Mce1 protein complex initiates rapid induction of transcription of genes involved in substrate trafficking. Genes Immun 13, 496–502 (2012). https://doi.org/10.1038/gene.2012.24

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  • DOI: https://doi.org/10.1038/gene.2012.24

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