LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of

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Mycobacterium tuberculosis is among the leading infectious causes of human death. A better understanding of its virulence mechanisms is needed to facilitate development of novel therapeutics and a preventative vaccine. Lipoarabinomannan (LAM), an abundant surface-exposed lipoglycan, is believed to be a critical virulence determinant for intracellular survival and latency of M. tuberculosis. In vitro experiments with purified LAM have led to a model in which surface-exposed LAM binds to macrophage mannose receptor and facilitates bacterium entry, inhibition of phagosome-lysosome fusion, and modulation of innate immune responses. However, confirmation of these findings in vivo has not been possible due to the essentiality of genes involved in the LAM biosynthetic pathway. It was recently shown that LprG, a cell envelope lipoprotein, binds to the acyl groups of lipoglycan, but the role of LprG in LAM biosynthesis and localization remains unknown. Here, using an M. tuberculosis lprG mutant and a novel cell-imprinting assay, we show that LprG is essential for normal surface expression of LAM and virulence of M. tuberculosis attributed to LAM. Our study provides new insights into the mechanism of surface expression of LAM and confirms the essential role surface LAM serves in pathogenesis of M. tuberculosis.

Vyšlo v časopise: LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004376
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004376

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