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Streptococcus is a genus of gram-positive coccus or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales, in the phylum Bacillota. Cell division in streptococci occurs along a single axis, so as they grow, they tend to form pairs or chains that may appear bent or twisted. This differs from staphylococci, which divide along multiple axes, thereby generating irregular, grape-like clusters of cells. Most streptococci are oxidase-negative and catalase-negative, and many are facultative anaerobes.
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 that tend to link in chains. They are clinically important for humans, as they are an infrequent, but usually pathogenic, part of the skin microbiota that can cause Group A streptococcal infection. S. pyogenes is the predominant species harboring the Lancefield group A antigen, and is often called group A Streptococcus (GAS). However, both Streptococcus dysgalactiae and the Streptococcus anginosus group can possess group A antigen as well. Group A streptococci, when grown on blood agar, typically produce small (2–3 mm) zones of beta-hemolysis, a complete destruction of red blood cells. The name group A (beta-hemolytic) Streptococcus is thus also used.
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, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.
Nelfinavir, sold under the brand name Viracept, is an antiretroviral medication used in the treatment of HIV/AIDS. Nelfinavir belongs to the class of drugs known as protease inhibitors (PIs) and like other PIs is almost always used in combination with other antiretroviral drugs.
Hemolysis is the breakdown of red blood cells. The ability of bacterial colonies to induce hemolysis when grown on blood agar is used to classify certain microorganisms. This is particularly useful in classifying streptococcal species. A substance that causes hemolysis is a hemolysin.
Virulence factors are cellular structures, molecules and regulatory systems that enable microbial pathogens to achieve the following:
Adenylate cyclase toxin is a virulence factor produced by some members of the genus Bordetella. Together with the pertussis toxin it is the most important virulence factor of the causative agent of whooping cough, Bordetella pertussis. Bordetella bronchiseptica and Bordetella parapertussis, also able to cause pertussis-like symptoms, also produce adenylate cyclase toxin. It is a toxin secreted by the bacteria to influence the host immune system.
Tetanolysin is a toxin produced by Clostridium tetani bacteria. Its function is unknown, but it is believed to contribute to the pathogenesis of tetanus. The other C. tetani toxin, tetanospasmin, is more definitively linked to tetanus. It is sensitive to oxygen.
Cytolysin refers to the substance secreted by microorganisms, plants or animals that is specifically toxic to individual cells, in many cases causing their dissolution through lysis. Cytolysins that have a specific action for certain cells are named accordingly. For instance, the cytolysins responsible for the destruction of red blood cells, thereby liberating hemoglobins, are named hemolysins, and so on. Cytolysins may be involved in immunity as well as in venoms.
Pore-forming proteins are usually produced by bacteria, and include a number of protein exotoxins but may also be produced by other organisms such as apple snails that produce perivitellin-2 or earthworms, who produce lysenin. They are frequently cytotoxic, as they create unregulated pores in the membrane of targeted cells.
Hemolysins or haemolysins are lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. Although the lytic activity of some microbe-derived hemolysins on red blood cells may be of great importance for nutrient acquisition, many hemolysins produced by pathogens do not cause significant destruction of red blood cells during infection. However, hemolysins are often capable of lysing red blood cells in vitro.
Listeriolysin O (LLO) is a hemolysin produced by the bacterium Listeria monocytogenes, the pathogen responsible for causing listeriosis. The toxin may be considered a virulence factor, since it is crucial for the virulence of L. monocytogenes.
The Membrane Attack Complex/Perforin (MACPF) superfamily, sometimes referred to as the MACPF/CDC superfamily, is named after a domain that is common to the membrane attack complex (MAC) proteins of the complement system and perforin (PF). Members of this protein family are pore-forming toxins (PFTs). In eukaryotes, MACPF proteins play a role in immunity and development.
Alpha-toxin, also known as alpha-hemolysin (Hla), is the major cytotoxic agent released by bacterium Staphylococcus aureus and the first identified member of the pore forming beta-barrel toxin family. This toxin consists mostly of beta-sheets (68%) with only about 10% alpha-helices. The hly gene on the S. aureus chromosome encodes the 293 residue protein monomer, which forms heptameric units on the cellular membrane to form a complete beta-barrel pore. This structure allows the toxin to perform its major function, development of pores in the cellular membrane, eventually causing cell death.
Anti-streptolysin O 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" in the name stands for oxygen-labile; the other related toxin being oxygen-stable streptolysin-S. The main function of streptolysin O is to cause hemolysis —in particular, beta-hemolysis.
Clostridioides difficile toxin B (TcdB) is a cytotoxin produced by the bacteria Clostridioides difficile. It is one of two major kinds of toxins produced by C. difficile, the other being a related enterotoxin. Both are very potent and lethal.
Streptococcus dysgalactiae is a gram positive, beta-haemolytic, coccal bacterium belonging to the family Streptococcaceae. It is capable of infecting both humans and animals, but is most frequently encountered as a commensal of the alimentary tract, genital tract, or less commonly, as a part of the skin flora. The clinical manifestations in human disease range from superficial skin-infections and tonsillitis, to severe necrotising fasciitis and bacteraemia. The incidence of invasive disease has been reported to be rising. Several different animal species are susceptible to infection by S. dysgalactiae, but bovine mastitis and infectious arthritis in lambs have been most frequently reported.
The RTX toxin superfamily is a group of cytolysins and cytotoxins produced by bacteria. There are over 1000 known members with a variety of functions. The RTX family is defined by two common features: characteristic repeats in the toxin protein sequences, and extracellular secretion by the type I secretion systems (T1SS). The name RTX refers to the glycine and aspartate-rich repeats located at the C-terminus of the toxin proteins, which facilitate export by a dedicated T1SS encoded within the rtx operon.
Streptococcal pyrogenic exotoxins also known as erythrogenic toxins, are exotoxins secreted by strains of the bacterial species Streptococcus pyogenes. SpeA and speC are superantigens, which induce inflammation by nonspecifically activating T cells and stimulating the production of inflammatory cytokines. SpeB, the most abundant streptococcal extracellular protein, is a cysteine protease. Pyrogenic exotoxins are implicated as the causative agent of scarlet fever and streptococcal toxic shock syndrome. There is no consensus on the exact number of pyrogenic exotoxins. Serotypes A-C are the most extensively studied and recognized by all sources, but others note up to thirteen distinct types, categorizing speF through speM as additional superantigens. Erythrogenic toxins are known to damage the plasma membranes of blood capillaries under the skin and produce a red skin rash. Past studies have shown that multiple variants of erythrogenic toxins may be produced, depending on the strain of S. pyogenes in question. Some strains may not produce a detectable toxin at all. Bacteriophage T12 infection of S. pyogenes enables the production of speA, and increases virulence.
The thiol-activated Cholesterol-dependent Cytolysin(CDC) family 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 are secreted as water-soluble monomers of 50-70 kDa, that when bound to the target cell, form a circular homo-oligomeric complex containing as many as 40 monomers. Through multiple conformational changes, the β-barrel transmembrane structure is formed and inserted into the target cell membrane. The presence of cholesterol in the target membrane is required for pore formation, though the presence of cholesterol is not required by all CDCs for binding. For example, intermedilysin secreted by Streptococcus intermedius will bind only to target membranes containing a specific protein receptor, independent of the presence of cholesterol, but cholesterol is required by intermedilysin for pore formation. While the lipid environment of cholesterol in the membrane can affect toxin binding, the exact molecular mechanism that cholesterol regulates the cytolytic activity of the CDC is not fully understood.
References
- ↑ "streptolysin" at Dorland's Medical Dictionary
- ↑ Streptolysin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
