title: Characterizing virulence-specific perturbations in the mitochondrial function of macrophages infected with Mycobacterium tuberculosis.
abstract: To probe how the pathogen Mycobacterium tuberculosis controls host cellular death pathways, we compared mitochondrial responses in human macrophages infected either with the avirulent mycobacterial strain H37Ra, or its virulent counterpart H37Rv. Following H37Ra infection, induction of the apoptotic response was foreshadowed by the early suppression of stress-induced mitochondrial activity. In contrast, mitochondria in H37Rv-infected cells displayed robust activity with increased membrane potential and ATP synthesis. An examination of the mitochondrial proteome revealed that attenuation of mitochondrial function was also coupled with the vigorous activation of bactericidal mechanisms in H37Ra-infected cells. In contrast, augmentation of mitochondrial activity by H37Rv enabled manipulation of host cellular mechanisms to inhibit apoptosis on the one hand, while ensuring fortification against anti-microbial pathways on the other. These results thus provide novel insights into the molecular interplay that facilitates adaptation of virulent mycobacteria within the hostile intracellular milieu of the host macrophage.
authors: Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi - 110067, India.
authors: Shilpa
authors: S
authors: Jamwal
authors: Mukul Kumar
authors: MK
authors: Midha
authors: Hirdya Narain
authors: HN
authors: Verma
authors: Atanu
authors: A
authors: Basu
authors: Kanury V S
authors: KV
authors: Rao
authors: Venkatasamy
authors: V
authors: Manivel
mesh_terms: D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D055032:Electron Microscope Tomography; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000472:pathogenicity*; D020543:Proteome / Q000378:metabolism; D012703:Serotyping; D014774:Virulence
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D020543:Proteome; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate