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FEBS Lett. 2016 Nov;590(21):3800-3819. doi: 10.1002/1873-3468.12273. Epub 2016 Jul 13.

Mycobacterium tuberculosis lipoproteins in virulence and immunity - fighting with a double-edged sword.

Author information

1
Institute of Medical Microbiology, University of Zurich, Switzerland.

Abstract

Bacterial lipoproteins are secreted membrane-anchored proteins characterized by a lipobox motif. This lipobox motif directs post-translational modifications at the conserved cysteine through the consecutive action of three enzymes: Lgt, LspA and Lnt, which results in di- or triacylated forms. Lipoproteins are abundant in all bacteria including Mycobacterium tuberculosis and often involved in virulence and immunoregulatory processes. On the one hand, disruption of the biosynthesis pathway of lipoproteins leads to attenuation of M. tuberculosis in vivo, and mycobacteria deficient for certain lipoproteins have been assessed as attenuated live vaccine candidates. On the other hand, several mycobacterial lipoproteins form immunodominant antigens which promote an immune response. Some of these have been explored in DNA or subunit vaccination approaches against tuberculosis. The immune recognition of specific lipoproteins, however, might also benefit long-term survival of M. tuberculosis through immune modulation, while others induce protective responses. Exploiting lipoproteins as vaccines is thus a complex matter which requires deliberative investigation. The dual role of lipoproteins in the immunity to and pathogenicity of mycobacteria is discussed here.

KEYWORDS:

immune modulation; lipoprotein; post-translational modification; tuberculosis; vaccine; virulence

PMID:
27350117
DOI:
10.1002/1873-3468.12273
[Indexed for MEDLINE]
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