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Microbes Infect. 2017 Nov;19(11):515-526. doi: 10.1016/j.micinf.2017.06.008. Epub 2017 Jul 6.

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

Author information

1
National Center for Biological Sciences, GKVK, Bellary Road, Bengaluru, India. Electronic address: varadha@ncbs.res.in.
2
Scientific Institute of Public Health (WIV-ISP (Site Ukkel)), Juliette Wytsmanstraat 14, 1050 Brussels, Belgium.
3
National Center for Biological Sciences, GKVK, Bellary Road, Bengaluru, India.
4
Biozentrum, University of Basel, Klingelbergstrasse 70, Basel, Switzerland.
5
Department of Molecular Biology and Microbiology, Department of Molecular Biology and Microbiology, Case Western Reserve University, 10900 Euclid Ave, LC 4860, Cleveland, OH, USA.
6
Department of Biomedicine, University Hospital, Hebelstrasse 20, 4056, Basel, Switzerland.

Abstract

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.

KEYWORDS:

In vivo; Lysosomes; Pathogenesis; PknG; Survival; Tuberculosis

PMID:
28689009
DOI:
10.1016/j.micinf.2017.06.008
[Indexed for MEDLINE]

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