The role of histamine in the intracellular survival of Mycobacterium bovis BCG

New strategies are required to reduce the worldwide burden of tuberculosis. Intracellular survival and replication of Mycobacterium tuberculosis after macrophage phagocytosis is a fundamental step in the complex host–pathogen interactions that lead to granuloma formation and disease. Greater understanding of how the bacterium survives and thrives in these environments will inform novel drug and vaccine discovery programs. Here, we use in-depth RNA sequencing of Mycobacterium bovis BCG from human THP-1 macrophages to describe the mycobacterial adaptations to the intracellular environment. We identify 329 significantly differentially regulated genes, highlighting cholesterol catabolism, the methylcitrate cycle and iron homeostasis as important for mycobacteria inside macrophages. Examination of multi-functional gene families revealed that 35 PE/PPE genes and five cytochrome P450 genes were upregulated 24 h after infection, highlighting pathways of potential significance. Comparison of the intracellular transcriptome to gene essentiality and immunogenicity studies identified 15 potential targets that are both required for intracellular survival and induced on infection, and eight upregulated genes that have been demonstrated to be immunogenic in TB patients. Further insight into these new and established targets will support drug and vaccine development efforts.

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The Role of Glutamine Oxoglutarate Aminotransferase and Glutamate Dehydrogenase in Nitrogen Metabolism in Mycobacterium bovis BCG

PLoS ONE ◽

10.1371/journal.pone.0084452 ◽

2013 ◽

Vol 8 (12) ◽

pp. e84452 ◽

Cited By ~ 10

Author(s):

Albertus J. Viljoen ◽

Catriona J. Kirsten ◽

Bienyameen Baker ◽

Paul D. van Helden ◽

Ian J. F. Wiid

Keyword(s):

Glutamate Dehydrogenase ◽

Nitrogen Metabolism ◽

Mycobacterium Bovis ◽

Mycobacterium Bovis Bcg

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ESAT-6 regulates autophagous response through SOD-2 and as a result induces intracellular survival of Mycobacterium bovis BCG

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics ◽

10.1016/j.bbapap.2020.140470 ◽

2020 ◽

Vol 1868 (10) ◽

pp. 140470

Author(s):

Shivraj M. Yabaji ◽

Ekta Dhamija ◽

Alok K. Mishra ◽

Kishore K. Srivastava

Keyword(s):

Mycobacterium Bovis ◽

Intracellular Survival ◽

Mycobacterium Bovis Bcg

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Mycobacterium bovis BCG promotes IL-10 expression by establishing a SYK/PKCα/β positive autoregulatory loop that sustains STAT3 activation

Pathogens and Disease ◽

10.1093/femspd/ftz032 ◽

2019 ◽

Vol 77 (3) ◽

Author(s):

Tomás Villaseñor ◽

Edgardo Madrid-Paulino ◽

Rafael Maldonado-Bravo ◽

Leonor Pérez-Martínez ◽

Gustavo Pedraza-Alva

Keyword(s):

Mycobacterium Bovis ◽

Feedback Loop ◽

Expression Profiles ◽

Adaptive Immune Response ◽

Gene Expression Profiles ◽

Cytokine Gene Expression ◽

Mycobacterium Bovis Bcg ◽

Adaptive Immune

ABSTRACT Mycobacterium ensures its survival inside macrophages and long-term infection by subverting the innate and adaptive immune response through the modulation of cytokine gene expression profiles. Different Mycobacterium species promote the expression of TGFβ and IL-10, which, at the early stages of infection, block the formation of the phagolysosome, thereby securing mycobacterial survival upon phagocytosis, and at later stages, antagonize IFNγ production and functions. Despite the key role of IL-10 in mycobacterium infection, the signal transduction pathways leading to IL-10 expression in infected macrophages are poorly understood. Here, we report that Mycobacterium bovis BCG promotes IL-10 expression and cytokine production by establishing a SYK/PKCα/β positive feedback loop that leads to STAT3 activation.

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