Streptolysins
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Streptolysins are two
hemolytic Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo o ...
exotoxin An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, simi ...
s from ''
Streptococcus ''Streptococcus'' is a genus of gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occurs ...
''. Types include streptolysin O (SLO; ''slo''), which is oxygen-labile, and streptolysin S (SLS; ''sagA''), which is oxygen-stable. SLO is part of the
thiol-activated cytolysin The thiol-activated Cholesterol-dependent Cytolysin (CDC) familyTC# 1.C.12 is a member of the MACPF superfamily. Cholesterol dependent cytolysins are a family of β-barrel pore-forming exotoxins that are secreted by gram-positive bacteria. CDCs ...
family. It is hemolytically active only in a reversibly reduced state. It is antigenic, so its antibody
antistreptolysin O Anti-streptolysin O (ASO or ASLO) is the antibody made against streptolysin O, an immunogenic, oxygen-labile streptococcal hemolytic exotoxin produced by most strains of group A and many strains of groups C and G ''Streptococcus'' bacteria. The ...
can be detected in an
antistreptolysin O titre Anti-streptolysin O (ASO or ASLO) is the antibody made against streptolysin O, an immunogenic, oxygen-labile streptococcal hemolytic exotoxin produced by most strains of group A and many strains of groups C and G ''Streptococcus'' bacteria. The "O ...
. SLS is stable in the presence of oxygen. It is not antigenic due to its small size. It is sometimes considered a
bacteriocin Bacteriocins are proteinaceous or peptidic toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain(s). They are similar to yeast and paramecium killing factors, and are structurally, functionally, and ec ...
due to similarities in the synthesis pathway.


Streptolysin O

Streptolysin O (SLO; ''slo),'' is a bacterial toxin that has four
protein domains In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
which is known to make the plasma membranes in animal cells permeable. It does this by creating pore complexes within the membrane by first binding a monomer to the cholesterol found in the target membrane and then forming an
oligomeric In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...
transmembrane pore. This toxin excreted by a
Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...
''
Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus ''Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They are ...
,'' under the classification of
Thiol-activated cytolysin The thiol-activated Cholesterol-dependent Cytolysin (CDC) familyTC# 1.C.12 is a member of the MACPF superfamily. Cholesterol dependent cytolysins are a family of β-barrel pore-forming exotoxins that are secreted by gram-positive bacteria. CDCs ...
or CDCs. In order for Streptolysin O to work effectively, it needs a significant amount of cholesterol to be present in the target membrane. Unlike other
Cholesterol-dependent cytolysin The thiol-activated Cholesterol-dependent Cytolysin (CDC) familyTC# 1.C.12 is a member of the MACPF superfamily. Cholesterol dependent cytolysins are a family of β-barrel pore-forming exotoxins that are secreted by gram-positive bacteria. CDCs ...
s, SLO contains a 60
Amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
N-terminal domain that makes it easier to identify.
Human serum albumin Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric. Albumin ...
has been demonstrated to neutralize the cytotoxic and hemolytic effects of SLO through its binding in a non-conventional site located in domain II, previously reported to interact also with ''C. difficile'' toxins. This toxin contains highly antigenic effects which causes it to produce the antibody
anti-streptolysin O Anti-streptolysin O (ASO or ASLO) is the antibody made against streptolysin O, an immunogenic, oxygen-labile streptococcal hemolytic exotoxin produced by most strains of group A and many strains of groups C and G ''Streptococcus'' bacteria. The ...
. Clinically, the presence of these antibodies can indicate a recent
Group A streptococcal infection Group A streptococcal infections are a number of infections with ''Streptococcus pyogenes'' a group A streptococcus (GAS). ''S. pyogenes'' is a species of beta-hemolytic gram-positive bacteria that is responsible for a wide range of infections tha ...
. Streptolysin O is also known to facilitate apoptosis in
Keratinocyte Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the stratum basale, basal layer (''str ...
s. It is able to do this by translocating
NAD+ glycohydrolase In enzymology, a NAD+ glycohydrolase () is an enzyme that catalyzes the chemical reaction :NAD+ + H2O \rightleftharpoons ADP-ribose + nicotinamide Thus, the two substrates of this enzyme are NAD+ and H2O, whereas its two products are ADP-r ...
(SPN) across the target cells membrane. It then removes the N-terminal domain which stops SPN translocation leading to SPN mediated apoptosis.


Group A ''Streptococcus'' infections

Group A streptococcal infection Group A streptococcal infections are a number of infections with ''Streptococcus pyogenes'' a group A streptococcus (GAS). ''S. pyogenes'' is a species of beta-hemolytic gram-positive bacteria that is responsible for a wide range of infections tha ...
s are responsible for 517,000 deaths annually across the world. Not much is known about the exact mechanism of action of these infections however, once the infection is present within the cells it can cause devastating effects. When tested in human endometrium cells, 50% of the cells were killed within the first two hours as a result of processes stimulated by Streptolysin O and SpeB proteases. It has also been observed that both Steptolysin O and SpeB protease limit the innate immune response.


Streptolysin S

Streptolysin S (SLS; ''sagA''), is a cytolytic
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...
factor which is a member of the thiazole/oxadole-modified microcin (TOMM) family. This cytolysin is a
post-translationally modified Post-translational modification (PTM) is the covalent and generally enzyme, enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by r ...
peptide was synthesized through a natural evolutionary pathway. SLS is responsible for ''Streptococcus pyogenes β-hemolytic appearance when grown on blood agar plates. Its biosynthesis is not fully known however, it is a critical virulence factor for ''Streptococcus pyogenes'' infections. SLS brings about its virulence by damaging soft tissue and it can also act as a signaling molecule. When introduced to a host it will affect its phagocytes and also help to introduce GAS across the skin barrier.


References

Bacterial toxins Hematology Streptococcal proteins Virulence factors {{biochem-stub