Official Full Name
α-Hemolysin
Background
α-Hemolysin is a 33 kDa extracellular protein secreted by most strains of pathogenic Staphylococcus aureus. It is selectively hemolytic and has a marked preference for rabbit red blood cells. It induces dermonecrosis, spastic muscle paralysis, and it is lethal for laboratory animals. The toxin must be in the monomeric form to initially bind to a membrane and specific receptors are not required for binding. Upon binding to biological membranes and/or artificial membranes, self-oligomerization occurs, resulting in ring structures (hexameric aggregates) believed to represent transmembrane pores, which are permeable to ions and small metabolites.
Synonyms
α-Hemolysin; 94716-94-6; α-Toxin
Hemolysin is a lipid and protein that causes red blood cell lysis by destroying cell membranes. Although the lysis activity of some microbial hemolysin on red blood cells may be very important for nutrient acquisition, many hemolysins produced by pathogens will not cause significant damage to red blood cells during infection. However, hemolysin is usually able to lyse red blood cells in vitro.
Figure 1. Protein structure of α-Hemolysin.
Introductions
In terms of serology and bacteriology, hemolysin will damage the red blood cell membrane and cause hemoglobin to overflow, that is, the biological factor that can produce hemolytic reaction is called hemolysin. Antibodies with strong complement binding, streptococcal hemolysin O (SLO) of hemolytic streptococci and other bacteria secrete toxins with hemolytic effect, all belong to this type of factor. Alpha-hemolysin is an exotoxin secreted by Staphylococcus aureus, one of its main virulence factors, and has good immunogenicity. Alpha-hemolysin has a hemolytic effect on many mammalian red blood cells. The mechanism is that toxin molecules insert into the hydrophobic area of the red blood cell membrane to form micropores, destroy the integrity of the cell membrane, and cause cell lysis. After mutating histidine at position 35 of Α-hemolysin to alanine, the mutant loses its hemolytic activity and is not toxic, but still retains its immunogenicity. It can be directly used to immunize animals. It is Staphylococcus aureus One of the important candidate proteins for subunit vaccines.
Function
Alpha-hemolysin can damage the red blood cells and platelets of humans and animals, and promote the contraction and spasm of small blood vessel smooth muscles, capillary blood flow block and ischemic necrosis. The cell and species specificity of α-hemolysin is mainly reflected in that it relies on cholesterol and sphingomyelin, disaggregated metalloprotease ADAM10, caveolin 1 (cAveo-LIn-1) to exert hemolysis. Studies have found that if cholesterol and sphingomyelin in rabbit red blood cells are decomposed, the affinity of A-hemolysin to rabbit red blood cells will be reduced, which shows that A-hemolysin binds with cholesterol and sphingomyelin on rabbit red blood cells to exert hemolysis. But in fact, the rabbit red blood cell membrane contains only a small amount of cholesterol and sphingomyelin.
Apoptosis caused by hemolysin
The α-hemolysin, β-hemolysin, and γ-hemolysin secreted by Staphylococcus aureus activate NLRP3 to activate cAsPAse-1, which can act as a protease and cause cell swelling and necrosis. Whether δ hemolysin has this effect has not been reported. Studies have found that α-hemolysin can also secrete TNF-α and activate cAsPAse-8 and cAsPAse-3, thereby causing cell apoptosis. However, apoptosis cannot be completed after adding TNF-α antibody, cAsPAse-3 and cAsPAse-8 inhibitors blocked, it suggests that there are other apoptosis pathways. The alpha-hemolysin of Staphylococcus aureus can not only actively kill tumor cells, but also secrete membranous vesicles, thereby promoting cell apoptosis.
Study on apoptosis caused by hemolysin
The α-hemolysin, β-hemolysin, and γ-hemolysin secreted by Staphylococcus aureus activate NLRP3 to activate cAsPAse-1, which can act as a protease and cause cell swelling and necrosis. Whether δ hemolysin has this effect has not been reported. Studies have found that α-hemolysin can also secrete TNF-α and activate cAsPAse-8 and cAsPAse-3, thereby causing cell apoptosis. However, apoptosis cannot be completed after adding TNF-α antibody, cAsPAse-3 and cAsPAse-8 inhibitors blocked, it suggests that there are other apoptosis pathways. The alpha-hemolysin of Staphylococcus aureus can not only actively kill tumor cells, but also secrete membranous vesicles, thereby promoting cell apoptosis.
Reference
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Song L.; et al. Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science. 1996, 274 (5294): 1859–66.