Streptolysin

Streptolysins are two hemolytic exotoxins from Streptococcus.[1][2] Types include streptolysin O (SLO; slo), which is oxygen-labile, and streptolysin S (SLS; sagA), which is oxygen-stable.[3]

Streptolysin O
Identifiers
OrganismStreptococcus pyogenes serotype M1
Symbolslo
UniProtP0C0I3
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StructuresSwiss-model
DomainsInterPro
Streptolysin S
Identifiers
OrganismStreptococcus pyogenes serotype M4 (strain MGAS10750)
SymbolsagA
UniProtQ1J7I0
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StructuresSwiss-model
DomainsInterPro

SLO is part of the thiol-activated cytolysin family.[4] It is hemolytically active only in a reversibly reduced state. It is antigenic, so its antibody antistreptolysin O can be detected in an antistreptolysin O titre.

SLS is stable in the presence of oxygen. It is not antigenic due to its small size. It is sometimes considered a bacteriocin due to similarities in the synthesis pathway.[5]

Streptolysin O

Streptolysin O (SLO; slo), is a bacterial toxin that has four protein domains 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 transmembrane pore.[6] This toxin excreted by a Gram-positive bacteria Streptococcus pyogenes, under the classification of Thiol-activated cytolysin 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 cytolysins, SLO contains a 60 Amino acid N-terminal domain that makes it easier to identify.

Human serum 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.[7]

This toxin contains highly antigenic effects which causes it to produce the antibody anti-streptolysin O. Clinically, the presence of these antibodies can indicate a recent Group A streptococcal infection. Streptolysin O is also known to facilitate apoptosis in Keratinocytes. It is able to do this by translocating NAD+ glycohydrolase (SPN) across the target cells membrane. It then removes the N-terminal domain which stops SPN translocation leading to SPN mediated apoptosis.[8]

Group A Streptococcus infections

Group A streptococcal infections 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.[9]

Streptolysin S

Streptolysin S (SLS; sagA), is a cytolytic virulence factor which is a member of the thiazole/oxadole-modified microcin (TOMM) family. This cytolysin is a post-translationally modified 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.[10] 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.[11]

References
  1. "streptolysin" at Dorland's Medical Dictionary
  2. Streptolysin at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. Sierig G, Cywes C, Wessels MR, Ashbaugh CD (January 2003). "Cytotoxic effects of streptolysin o and streptolysin s enhance the virulence of poorly encapsulated group a streptococci". Infection and Immunity. 71 (1): 446–55. doi:10.1128/IAI.71.1.446-455.2003. PMC 143243. PMID 12496195.
  4. Billington SJ, Jost BH, Songer JG (January 2000). "Thiol-activated cytolysins: structure, function and role in pathogenesis". FEMS Microbiology Letters. 182 (2): 197–205. doi:10.1111/j.1574-6968.2000.tb08895.x. PMID 10620666.
  5. Lee SW, Mitchell DA, Markley AL, Hensler ME, Gonzalez D, Wohlrab A, et al. (April 2008). "Discovery of a widely distributed toxin biosynthetic gene cluster". Proceedings of the National Academy of Sciences of the United States of America. 105 (15): 5879–84. doi:10.1073/pnas.0801338105. PMC 2311365. PMID 18375757.
  6. Abdel Ghani EM, Weis S, Walev I, Kehoe M, Bhakdi S, Palmer M (November 1999). "Streptolysin O: inhibition of the conformational change during membrane binding of the monomer prevents oligomerization and pore formation". Biochemistry. 38 (46): 15204–11. doi:10.1021/bi991678y. PMID 10563803.
  7. Vita GM, De Simone G, Leboffe L, Montagnani F, Mariotti D, Di Bella S, et al. (2020-12-08). "Human Serum Albumin Binds Streptolysin O (SLO) Toxin Produced by Group A Streptococcus and Inhibits Its Cytotoxic and Hemolytic Effects". Frontiers in Immunology. 11: 507092. doi:10.3389/fimmu.2020.507092. PMC 7752801. PMID 33363530.
  8. Reglinski M, Sriskandan S (2015). "Streptococcus pyogenes". Molecular Medical Microbiology. Elsevier. pp. 675–716. doi:10.1016/b978-0-12-397169-2.00038-x. ISBN 978-0-12-397169-2.
  9. Weckel A, Guilbert T, Lambert C, Plainvert C, Goffinet F, Poyart C, et al. (February 2021). "Streptococcus pyogenes infects human endometrium by limiting the innate immune response". The Journal of Clinical Investigation. 131 (4). bioRxiv 10.1101/713875. doi:10.1172/jci130746. PMC 7880408. PMID 33320843.
  10. Maxson T, Deane CD, Molloy EM, Cox CL, Markley AL, Lee SW, Mitchell DA (May 2015). "HIV protease inhibitors block streptolysin S production". ACS Chemical Biology. 10 (5): 1217–26. doi:10.1021/cb500843r. PMC 4574628. PMID 25668590.
  11. Molloy EM, Cotter PD, Hill C, Mitchell DA, Ross RP (August 2011). "Streptolysin S-like virulence factors: the continuing sagA". Nature Reviews. Microbiology. 9 (9): 670–81. doi:10.1038/nrmicro2624. PMC 3928602. PMID 21822292.
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