Phthiocerol dimycocerosates of M. tuberculosis participate in macrophage invasion by inducing changes in the organization of plasma membrane lipids.

PLoS Pathogens
Catherine Astarie-DequekerChristophe Guilhot

Abstract

Phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), in particular during the early step of infection when bacilli encounter their host macrophages. However, their cellular and molecular mechanisms of action remain unknown. Using Mtb mutants deleted for genes involved in DIM biosynthesis, we demonstrated that DIM participate both in the receptor-dependent phagocytosis of Mtb and the prevention of phagosomal acidification. The effects of DIM required a state of the membrane fluidity as demonstrated by experiments conducted with cholesterol-depleting drugs that abolished the differences in phagocytosis efficiency and phagosome acidification observed between wild-type and mutant strains. The insertion of a new cholesterol-pyrene probe in living cells demonstrated that the polarity of the membrane hydrophobic core changed upon contact with Mtb whereas the lateral diffusion of cholesterol was unaffected. This effect was dependent on DIM and was consistent with the effect observed following DIM insertion in model membrane. Therefore, we propose that DIM control the invasion of macrophages by Mtb by targeting lipid organisation in the host membrane, thereby modifying its biophysical proper...Continue Reading

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Citations

Mar 24, 2011·Future Medicinal Chemistry·Kirsty J McLeanAndrew W Munro
Dec 21, 2012·Future Microbiology·Rebekka Steinmann, Petra Dersch
Jul 18, 2014·Cell Death & Disease·N AguilóJ Pardo
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Methods Mentioned

BETA
fluorescence microscopy
Confocal microscopy
dynamic light scattering
PCR
PMA
light microscopy
Fluorescence

Software Mentioned

FeliX32

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