title: Mycobacterium tuberculosisCpn60.2 (GroEL2) blocks macrophage apoptosis via interaction with mitochondrial mortalin.
abstract: Earlier studies suggested thatMycobacterium tuberculosis(Mtb) proteins exported within the host macrophage play an essential role in tuberculosis pathogenesis. In fact, Mtb proteins interact with and deactivate key regulators of many macrophage functions such as phago-lysosome fusion and antigen presentation, resulting in the intracellular persistence of pathogenic mycobacteria. Cpn60.2 is an abundant Mtb chaperone protein, restricted to cell cytoplasm and surface, that was reported to be essential for bacterial growth. Here, we provide evidence that once Mtb is ingested by the macrophage, Cpn60.2 is able to detach from the bacterial surface and crosses the phagosomal membrane towards mitochondria organelles. Once there, Cpn60.2 interacts with host mortalin, a member of the HSP 70 gene family that contributes to apoptosis modulation. In this regard, we showed that Cpn60.2 blocks macrophage apoptosis, a phenotype that is reversed when cells are pretreated with a specific mortalin inhibitor. Our findings have extended the current knowledge of the Mtb Cpn60.2 functions to add a strong anti-apoptotic activity dependent on its interaction with mitochondrial mortalin, which otherwise promotes Mtb survival in the hostile macrophage environment.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, British Columbia V6H 3Z6, Canada.
authors.forename: Sunil
authors.initials: S
authors.lastname: Joseph
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, British Columbia V6H 3Z6, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Yuen
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, British Columbia V6H 3Z6, Canada.
authors.forename: Vijender
authors.initials: V
authors.lastname: Singh
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vancouver Costal Health Research Institute, University of British Columbia, Vancouver, British Columbia V6H 3Z6, Canada hmama@mail.ubc.ca.
authors.forename: Zakaria
authors.identifier: http://orcid.org/0000-0001-5815-7068
authors.initials: Z
authors.lastname: Hmama
keywords: Host-pathogen interaction; Intra-cellular trafficking; Mycobacterial persistence; Phagosome