Mycobacterium tuberculosis Mce1 protein complex initiates rapid induction of transcription of genes involved in substrate trafficking.
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.
Department of Microbiology and Immunology, The Gade Institute, University of Bergen, Bergen, Norway. Ruth.Stavrum@Gades.uib.no
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Stavrum
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Valvatne
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Stavrum
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Riley
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Ulvestad
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Jonassen
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Doherty
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Grewal
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology*; D002460:Cell Line; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D008264:Macrophages / Q000382:microbiology / Q000502:physiology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity*; D015533:Transcriptional Activation; D059467:Transcriptome; D015854:Up-Regulation
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D050485:GABA Plasma Membrane Transport Proteins; C490439:Slc6a12 protein, mouse; C473802:mammalian cell entry protein Mce1A, Mycobacterium tuberculosis