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Pore Forming Toxins
Pore-forming proteins (PFTs, also known as pore-forming toxins) 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 (i.e., they kill cells), as they create unregulated pores in the membrane of targeted cells. Types PFTs can be divided into two categories, depending on the alpha-helical or beta-barrel architecture of their transmembrane channel that can consist either of * Alpha-pore-forming toxins ** e.g., Haemolysin E family, actinoporins, Corynebacterial porin B, Cytolysin A of ''E. coli''. * Beta-barrel pore-forming toxins ** e.g. α-hemolysin (Fig 1), PVL – Panton-Valentine leukocidin, various insecticidal toxins. Other categories: * Large beta-barrel pore-forming toxins ** MACPF and Cholesterol-dependent cytolysins (CDCs), gasdermin * Binary toxins ** e.g., Anthrax toxin, Pleurotolysi ...
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Staphylococcus Aureus Alpha Toxin
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. Function Alpha-toxin has been shown to play a role in pathogenesis of disease, as ''hly'' knockout strains show reductions in invasiveness and virulence. The dosage of toxin can result in two different modes of activity. Low concentrations of toxin bind to specific, but unidentified, cell surface receptors and form the heptameric pores. This pore allows the exchange of monovale ...
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Leukocidin
A leukocidin is a type of cytotoxin created by some types of bacteria (''Staphylococcus''). It is a type of pore-forming toxin. The model for pore formation is step-wise. First, the cytotoxin’s “S” subunit recognizes specific protein-containing receptors, or an integrin on the host cell’s surface. The S subunit then recruits a second, “F” subunit, and the two subunits dimerize on the surface of the host’s cell. After dimerization, oligomerization occurs. Finally, the oligomers, consisting of alternating S and F subunits, undergo a significant structural change and form a beta-barrel, that pierces through the host cell’s lipid bilayer. Leukocidins get their names by killing ("-cide") leukocytes. Leukocidins target phagocytes, natural killer cells, dendritic cells, and T lymphocytes and therefore targets both, innate and adaptive immune responses. Leukocidins fall into the category of bacterial invasin Invasins are a class of proteins associated with the penetration ...
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RTX Toxin
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 (repeats in toxin) 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. Structure and function RTX proteins range from 40 to over 600 kDa in size and all contain C-terminally located glycine and aspartate-rich repeat sequences of nine amino acids. The repeats contain the common sequence structure , (where X represents any amino acid), but the number of repeats varies within RTX protein family members. These consensus regions function as sites for Ca2+ binding, which facilitate folding of the RTX protein following export via an ...
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Aerolysin
In molecular biology, aerolysin is a cytolytic pore-forming toxin exported by ''Aeromonas hydrophila'', a Gram-negative bacterium associated with diarrhoeal diseases and deep wound infections. The mature toxin binds to eukaryotic cells and aggregates to form holes (approximately 3 nm in diameter) leading to the destruction of the membrane permeability barrier and osmotic lysis. The structure of proaerolysin has been determined to 2.8A resolution and shows the protoxin to adopt a novel fold. Images of an aerolysin oligomer derived from electron microscopy have helped to construct a model of the protein in its heptameric conformation, and to outline a mechanism by which this assembly might insert into lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...s to form io ...
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Hemolysin
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''. While most hemolysins are protein compounds, some are lipid biosurfactants. Properties Many bacteria produce hemolysins that can be detected in the laboratory. It is now believed that many clinically relevant fungi also produce hemolysins. Hemolysins can be identified by their ability to lyse red blood cells ''in vitro''. Not only are the erythrocytes affected by hemolysins, but there are also some effects among other blood cells, such as leucocytes (white blood cells). ''Escherichia coli'' hemolysin is potentially cytotoxic to monocytes ...
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Gramicidin
Gramicidin, also called gramicidin D, is a mix of ionophoric antibiotics, gramicidin A, B and C, which make up about 80%, 5%, and 15% of the mix, respectively. Each has 2 isoforms, so the mix has 6 different types of gramicidin molecules. They can be extracted from ''Brevibacillus brevis'' soil bacteria. Gramicidins are linear peptides with 15 amino acids. This is in contrast to unrelated gramicidin S, which is a cyclic peptide. Medical uses Gramicidins work as antibiotics against gram-positive bacteria like ''Bacillus subtilis'' and ''Staphylococcus aureus'', but not well against gram-negative ones like '' E. coli''. Gramicidins are used in medicinal lozenges for sore throat and in topical medicines to treat infected wounds. Gramicidins are often mixed with other antibiotics like tyrocidine and antiseptics. Gramicidins are also used in eye drops for bacterial eye infections. In drops, they are often mixed with other antibiotics like polymyxin B or neomycin. Multiple antibioti ...
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Anthrax Toxin
Anthrax toxin is a three-protein exotoxin secreted by virulent strains of the bacterium, ''Bacillus anthracis''—the causative agent of anthrax. The toxin was first discovered by Harry Smith in 1954. Anthrax toxin is composed of a cell-binding protein, known as protective antigen (PA), and two enzyme components, called edema factor (EF) and lethal factor (LF). These three protein components act together to impart their physiological effects. Assembled complexes containing the toxin components are endocytosed. In the endosome, the enzymatic components of the toxin translocate into the cytoplasm of a target cell. Once in the cytosol, the enzymatic components of the toxin disrupts various immune cell functions, namely cellular signaling and cell migration. The toxin may even induce cell lysis, as is observed for macrophage cells. Anthrax toxin allows the bacteria to evade the immune system, proliferate, and ultimately kill the host animal. Research on anthrax toxin also provides ...
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Gasdermin A
Gasdermin A is a protein that in humans is encoded by the GSDMA gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b .... References Further reading

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