Biological membranes are crucial for the survival of all living cells, serving as a dynamic barrier between the cell and its environment. They play a key role in various cellular functions, including molecular transport, intracellular signaling, and cell proliferation. The lipids in the membrane are appealing target for bacterial pathogens attempting to manipulate host cells. Microbial proteins, such as bacterial toxins and viral components, bind to the host cell membrane and introduce lipid membrane perturbations that contribute to the severity of the infection process.
Pore-forming protein toxins (PFTs) secreted by various bacterial pathogens are a type of membrane-damaging protein that form pores upon binding to the cell membrane. PFTs are synthesized as water-soluble monomeric molecules, and in contact with target cell membranes, they undergo conformational change and form membrane-inserted oligomeric pores.
Using a combination of cell biology, biochemistry, and structural biology approaches, we have recently discovered a previously unknown phenomenon of cell membrane tubulation by a α-PFT, MakA (motility-associated killing factor A), secreted by Vibrio cholerae.