Bacterial protein toxins and lipids: pore formation or toxin entry into cells

Abstract

Lipids are hydrophobic molecules which play critical functions in cells, in particular, they are essential constituents of membranes, whereas bacterial toxins are mainly hydrophilic proteins. All bacterial toxins interact first with their target cells by recognizing a surface receptor, which is either a lipid or a lipid derivative, or another compound but in a lipid environment. Most bacterial toxins are PFTs (pore‐forming toxins) which oligomerize and insert into the lipid bilayer. A common mechanism of action involves the formation of a β‐barrel structure, resulting from the assembly of individual β‐hairpin(s) from individual monomers. An essential step for intracellular active toxins is to translocate their enzymatic part into the cytosol. Some toxins use a translocation mechanism based on pore formation similar to that of PFTs, others undergo a yet unclear ‘chaperone’ process.

Bacterial protein toxins and lipids: role in toxin targeting and activity

“…After binding to a cell surface receptor, some toxins directly act on the cell membrane, whereas others enter cells and modify an intracellular target. Pore formation induced by toxins through the plasma membrane and translocation of toxin components across the lipid bilayer is discussed in the accompanying article in this issue of Biology of the Cell (Geny and Popoff, 2006). Here, we will discuss the other types of interaction between bacterial protein toxins and cell lipids, including lipids But even for protein toxin receptors, the lipid environment plays an important role in toxin-receptor interaction.…”

“…Indeed, anthrax toxins are binary toxins comprised of a receptorbinding component [PA (protective antigen)] which heptamerizes and forms a pore using endosomal vesicle membrane, thereby mediating the internalization of the enzymatic components EF (oedema factor) or LF (lethal factor) (Abrami et al, 2005;Leppla, 2006) (and see accompanying article in this issue, Geny and Popoff, 2006). PA recognizes protein cell surface receptors, such as TEM8 (tumour endothelial marker 8) and CMG2 (capillary morphogenesis 2).…”

Identification of a target protein of Hydra actinoporin-like toxin-1 (HALT-1) using GST affinity purification and SILAC-based quantitative proteomics

“…They are produced by a variety of organisms such as bacteria (Geny and Popoff, 2006), yeast-fungi (Bussey, 1991) and human (Voskoboinik et al, 2010). In sea anemones, a group of alpha helical-pore-forming toxins (α-PFTs) was isolated and named actinoporins (Ferlan and Lebez, 1974;Kem, 1988;Turk, 1991).…”

Membrane-translocating peptides and toxins: from nature to bedside

“…A detailed figure of these bacterial and animal cytolysins can be seen elsewhere. 1,7,8 Differing from preformed or not associated in solution two-component (mostly non-enzymatic) cytolysins, which cause cell lysis after oligomerization and pore formation, there are numerous binary enzymatically active toxins secreted by bacteria. These are known as 'bacterial binary toxins' and they have essentially one catalytic domain or chain ('A' moiety) and one receptor binding component ('B' moiety) that is single chain or multimeric.…”

“…-toxin and aerolysin), that are the result of the insertion of -barrel structures into the lipid bilayer. 1 Aerolysin, the preformed two-component cytolysin from culture supernatants of Aeromonas hydrophila, is constituted by four domains (1 to 4) that oligomeryze in a heptameric form on cell membrane after activation by endoproteases (trypsin or -chymotrypsin). Domains 1 and 2 recognize the receptor (GPI-anchored proteins), which are localized in lipid rafts, while domain 3 (and also domain 2) is responsible for oligomerization.…”