Survival of Mycobacterium tuberculosis and Mycobacterium bovis BCG in lysosomes in vivo

Sundaramurthy, Varadharajan and Korf, Hannelie and Singla, Ashima and Scherr, Nicole and Nguyen, Liem and Ferrari, Giorgio and Landmann, Regine and Huygen, Kris and Pieters, Jean. (2017) Survival of Mycobacterium tuberculosis and Mycobacterium bovis BCG in lysosomes in vivo. Microbes and Infection, 19 (11). pp. 515-526.

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Official URL: http://edoc.unibas.ch/55813/

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Mycobacterium tuberculosis is one of the most successful pathogens known, having infected more than a third of the global population. An important strategy for intracellular survival of pathogenic mycobacteria relies on their capacity to resist delivery to lysosomes, instead surviving within macrophage phagosomes. Several factors of both mycobacterial and host origin have been implicated in this process. However, whether or not this strategy is employed in vivo is not clear. Here we show that in vivo, following intravenous infection, M. tuberculosis and Mycobacterium bovis BCG initially survived by resisting lysosomal transfer. However, after prolonged infection the bacteria were transferred to lysosomes yet continued to proliferate. A M. bovis BCG mutant lacking protein kinase G (PknG), that cannot avoid lysosomal transfer and is readily cleared in vitro, was found to survive and proliferate in vivo. The ability to survive and proliferate in lysosomal organelles in vivo was found to be due to an altered host environment rather than changes in the inherent ability of the bacteria to arrest phagosome maturation. Thus, within an infected host, both M. tuberculosis and M. bovis BCG adapts to infection-specific host responses. These results are important to understand the pathology of tuberculosis and may have implications for the development of effective strategies to combat tuberculosis.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Biochemistry (Pieters)
UniBasel Contributors:Pieters, Jean
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:29 Nov 2017 15:49
Deposited On:23 Oct 2017 10:17

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