Abstract
Lipids dictate membrane properties to modulate lateral membrane organization, lipid/protein diffusion and lipid-protein interactions, thereby underpinning proper functioning of cells. Mycobacterium tuberculosis harnesses the power of its atypical cell wall lipids to impact immune surveillance machinery centered at the host cell membrane. However, the role of specific virulent lipids in altering host cellular functions by modulating membrane organization and the associated signaling response are still pertinent unresolved questions. Here, combining membrane biophysics and cell biology, we elucidate how virulent Mtb sulfoglycolipids hijack the host cell membrane, affecting its order, fluidity, and stiffness along with manipulating the linked cytoskeleton. The functional outcome of this perturbation was assayed by monitoring membrane-associated autophagy signaling. These actions form a part of the overall response to commandeer host membrane-associated immune processes during infection. The findings on the mechanism of action of Mtb lipids on host cell membrane structure and downstream signaling will deepen the collective understanding of their functional aspects in membrane-dictated bacterial survival, pathogenesis and drug resistance and reveal suitable membrane driven-therapeutic intervention points and diagnostic tools.