Schahl Adrien, Réat Valérie, Malaga Wladimir, Birbes Clément, Czaplicki Georges, Jolibois Franck, Yamamoto Eiji, Ramos Pascal, Milon Alain, Saurel Olivier, Atkinson R Andrew, Astarie-Dequeker Catherine, Guilhot Christophe, Ferré Guillaume, Chavent Matthieu, Haanappel Evert
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
LPCNO, UPS, CNRS (UMR 5215), Institut National des Sciences Appliquées (INSA), Université de Toulouse, Toulouse, France.
Biophys J. 2025 Aug 6. doi: 10.1016/j.bpj.2025.07.040.
Glycolipids from pathogenic Mycobacterium tuberculosis play important roles during the interaction of the pathogen with macrophages and can shape the host cell's immune response by modulating its membrane structure and function. Here, we study the phenolic glycolipids (PGLs) present in the envelope of some hypervirulent strains of Mycobacterium tuberculosis and their impact on model membranes. By a combination of molecular modeling and simulations, and solid-state NMR experiments, we show that PGLs, such as the structurally related lipid phthiocerol dimycocerosate, adopt a conical shape in lipid membranes, which destabilizes the lamellar membrane phase and promotes a transition to a nonlamellar inverted-hexagonal phase. Unlike phthiocerol dimycocerosate, in our simulations, PGL remains anchored to the phosphate groups of the lipid bilayer by its sugar-carrying extremity, preventing lipid flip-flop. These findings shed new light on a potential biophysical role of PGLs through modulation of the properties of the host cell's membrane, in addition to the recognition of its sugar moiety by host cell immune receptors.
来自致病性结核分枝杆菌的糖脂在该病原体与巨噬细胞相互作用过程中发挥重要作用，并且可通过调节宿主细胞膜结构和功能来塑造宿主细胞的免疫反应。在此，我们研究了某些高毒力结核分枝杆菌菌株包膜中存在的酚糖脂（PGLs）及其对模型膜的影响。通过分子建模与模拟以及固态核磁共振实验相结合的方法，我们表明，PGLs，如结构相关的脂质结核硬脂酸双分枝菌酸酯，在脂质膜中呈锥形，这会破坏层状膜相的稳定性并促进向非层状反六角相的转变。与结核硬脂酸双分枝菌酸酯不同，在我们的模拟中，PGL通过其携带糖的末端锚定在脂质双层的磷酸基团上，从而防止脂质翻转。这些发现除了揭示宿主细胞免疫受体对PGL糖部分的识别外，还通过调节宿主细胞膜特性为PGL潜在的生物物理作用提供了新的线索。
