Toxins pore-forming

Staphylococcal a-hemolysin is another widely studied pore-forming toxin. It is used by infectious bacteria to perforate host animal cells by a mechanism that is distinct from that of gramicidin. Several aspects of the stmcture and function of this heptameric protein complex have been smdied. 

Interestingly, certain other pore-forming toxins possess helix-bundle motifs that may participate in channel formation, in a manner similar to that proposed for colicin la. For example, the S-endotoxui produced by Bacillus thuringiensis is toxic to Coleoptera insects (beetles) and is composed of three domains, including a seven-helix bundle, a three-sheet domain, and a /3-sandwich. In the seven-helix bundle, helix 5 is highly hydrophobic, and the other six helices are amphipathic. In solution (Figure 10.32), the six amphipathic... 

Toxins that Attack the Cell Membrane Phospholipases and Pore-Forming Toxins 150... 

The prototype of a small pore-forming toxin is the S. aureus a-toxin, also called ct-hemolysin, that has been extensively investigated hy Bhakdi and coworkers. Monomers of ct-hemolysin (33 kDa) hind to the surface of erythrocytes, and after lateral diffusion within the lipid hilayer, seven monomers oligomerize to form pores in the cell membrane. The ct-hemolysin forms mushroom-shaped pores with an outer diameter of lOnm and an inner diameter of approximately 2.5 nm. Small molecules can pass through the pore and diffuse into/out of the cytosol, along with water. As a consequence of such movement, cell homeostasis is greatly disturbed and pushed into an unhealthy state. In animals, the a-hemolysin represents a major virulence factor of S. aureus which causes hemolysis as well as tissue destruction. ... 

When alamethicin is added to a ternary vesicle system comprising PDA, phospholipid, and lipopolysaccharide (LPS), the addition of polymyxin, an LPS-binding antibiotic, sensitizes the vesicles to alamethicin (Katz et al. 2003). Cholesterol-containing PDA liposomes have been used to colorimetrically detect streptolysin O, a cholesterol-dependent pore-forming toxin (Ma and Cheng 2005). 

Ma G, Cheng Q. Vesicular polydiacetylene sensor for colorimetric signaling of bacterial pore-forming toxin. Langmuir 2005 21 6123-6126. 

Several plausible hypotheses can explain this variability. Firstly, the venom contains a range of pore-forming toxins with varying conductances. Secondly, there is evidence that the make-up of the permeated membrane (Robello et al. 1984 Scheer et al. 1986 Krasilnikov and Sabirov 1992) and variations in lipid packing and order (Chanturia and Lishko 1992), but not the type of receptor present (Hlubek et al. 2000 Van Renterghem et al. 2000), can affect the properties of a-LTX channels. 

RTX Repeat in toxins pore-forming toxin of E. coli type (RTX toxin) also... 

Lashuel HA, Lansbury PT. Are amyloid disease caused by protein aggregates that mimic bacterial pore-forming toxins Quart. Rev. Biophys. 2006 39 167-201. 

Secondary reactions provoked by pore-forming toxins are very diverse, and are probably responsible for short- and long-range effects in the host organism (for review, see Bhakdi ef al., 1994). Locally, PFTs can counteract the host defense system directly by killing phagocytes and lymphocytes, and they promote spread of infections by their cytocidal action on tissue cells (see e.g. Bhakdi et al., 1994 Paton et al., 1993 Trifillis et al., 1994 Welch, 1991 Welch et al., 1995 Welch et al., 1981). Mediators, derived for example from arachidonic acid, will provoke inflammation. 

Bhakdi, S, Weller U, Walev I et al. (1993) A guide to the use of pore-forming toxins tor controlled permeabilization of cell membranes. In Med Microbiol Immunol 182 167-175. 

Walev I, Vollmer P, Palmer M et al. (1996) Pore-forming toxins trigger shedding of receptors for interleukin 6 and lipopolysaccharide. In Proc Natl Acad Sci USA 93 7882-7887. 

Permeabilized cells allow the study of intracellular processes in situ under conditions which are believed to be close to the physiological situation in intact cells. Permeabilization by bacterial pore-forming toxins, alpha-toxin and streptolysin O (SLO) is now a widely accepted approach in the functional analysis of intracellular organelles. 

Assay to Compare Biological Activity of Various Pore-Forming Toxins Using Rabbit Erythrocytes... 

---