A multidisciplinary consortium of researchers in the Toulouse area (IPBS-UMR5089-CNRS; LCPNO-INSA; IRSAMC-University Toulouse III Paul Sabatier) has revealed new biophysical effects of lipids present at the surface of the bacillus responsible for tuberculosis,Mycobacterium tuberculosis. The bacteria use these lipids to deform the membrane of macrophages, cells of the immune system, to promote their invasion. This study has recently been published in PNAS.
Artistic view of the biophysical action of DIM conical lipids (in purple) as well as other lipids (DLiPE in orange and tripalmitin in red) on the bilayer phase transition from lamellar (white lines in the background) to inverse hexagonal (curves and circles in the foreground). © Pierre-Yves Monnier
Despite progress in the prevention and management of tuberculosis, this infectious disease remains a major cause of death worldwide. It is therefore necessary to develop innovative research strategies to better understand the virulence mechanisms ofM. tuberculosis. Researchers from Toulouse focused on unusual lipids present in the envelope of the bacterium whose molecular mechanisms of action are still poorly understood. These lipids are especially difficult to study, due to their very hydrophobic nature and the difficulty of working with such pathogenic bacteria.
By combining 31P solid state NMR and multi-scale molecular modeling, the researchers have identified how these lipids deform different types of membranes. This phenomenon is closely related to the conical shape that these lipids adopt inside the macrophage membranes. The researchers also studied lipids of different structures and further validate that lipids with conical shapes improve the ability ofM. tuberculosisto invade human macrophages.
The combination of various experimental and modeling approaches at different scales has helped to highlight new biophysical properties of mycobacterial lipids that are closely related to the ability ofM. tuberculosisto invade macrophages. This work opens new perspectives to understand the biophysical effects of lipid virulence factors ofM. tuberculosisand their consequences for the outcome of the infection.
J. Augenstreich, E. Haanappel, G. Ferré, G. Czaplicki, F. Jolibois, N. Destainville, C. Guilhot, A. Milon, C. Astarie-Dequeker, M. Chavent, The Conical Shape of DIM Lipids PromotesMycobacterium tuberculosisInfection of Macrophages. Proc Natl Acad Sci U S A. 2019 Nov 22. pii: 201910368. doi: 10.1073/pnas.1910368116.
Matthieu Chavent |Matthieu.Chavent@ipbs.fr| 05 61 17 54 21
Catherine Astarie-Dequeker |Catherine.Astarie-Dequeker@ipbs.fr| 05 61 17 54 55
Alain Millon |Alain.Millon@ipbs.fr| 05 61 17 54 23
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