Mycobacterium tuberculosis lipoprotein LprG binds lipoarabinomannan and determines its cell envelope localization to control phagolysosomal fusion
In: PLoS Pathogens, Jg. 10 (2014-10-01), Heft 10
Online
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Zugriff:
Mycobacterium tuberculosis (Mtb) virulence is decreased by genetic deletion of the lipoprotein LprG, but the function of LprG remains unclear. We report that LprG expressed in Mtb binds to lipoglycans, such as lipoarabinomannan (LAM), that mediate Mtb immune evasion. Lipoglycan binding to LprG was dependent on both insertion of lipoglycan acyl chains into a hydrophobic pocket on LprG and a novel contribution of lipoglycan polysaccharide components outside of this pocket. An lprG null mutant (Mtb ΔlprG) had lower levels of surface-exposed LAM, revealing a novel role for LprG in determining the distribution of components in the Mtb cell envelope. Furthermore, this mutant failed to inhibit phagosome-lysosome fusion, an immune evasion strategy mediated by LAM. We propose that LprG binding to LAM facilitates its transfer from the plasma membrane into the cell envelope, increasing surface-exposed LAM, enhancing cell envelope integrity, allowing inhibition of phagosome-lysosome fusion and enhancing Mtb survival in macrophages.
Author Summary The causative agent of tuberculosis, Mycobacterium tuberculosis (Mtb), persists in phagosomes inside infected macrophages. Mtb expresses lipoarabinomannan (LAM), which inhibits fusion of phagosomes with lysosomes as a means for Mtb to evade host defense. LAM is present in the cell envelope, which surrounds Mtb and interfaces with the host, but its localization remains unclear. We show that LprG, an Mtb lipoprotein, binds LAM and controls its distribution in the cell envelope. A mutant strain of Mtb that lacks LprG has less LAM at the surface of the cell envelope. This decreases LAM-mediated inhibition of phagosome-lysosome fusion, thereby impairing an immune evasion mechanism. We propose that LprG facilitates transfer of LAM from the plasma membrane into the cell envelope, enhancing its interaction with the host and ability to regulate host defense. Our results reveal mechanisms that determine bacterial cell envelope function and influence host-pathogen interactions and pathogen evasion of host defense.
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Mycobacterium tuberculosis lipoprotein LprG binds lipoarabinomannan and determines its cell envelope localization to control phagolysosomal fusion
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Autor/in / Beteiligte Person: | Wearsch, Pamela A. ; McDonald, David ; Jackson, Mary ; Harding, Clifford V. ; Shukla, Supriya ; Banaei, Niaz ; Athman, Jaffre J. ; Richardson, Edward T. ; W. Henry Boom ; Shi, Libin |
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Zeitschrift: | PLoS Pathogens, Jg. 10 (2014-10-01), Heft 10 |
Veröffentlichung: | Public Library of Science (PLoS), 2014 |
Medientyp: | unknown |
ISSN: | 1553-7374 (print) ; 1553-7366 (print) |
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