Cytolysins

A second group of myotoxic toxins, found almost exclusively in the venoms of cobras, are the cytotoxins (often called cobratoxins, cytolysins, cardiotoxins, or direct lytic factors). These, rather than phospholipases, are almost certainly the primary cause of muscle damage following bites by cobras. Their mechanism of action is not properly known, but it is certainly the case that their action is potentiated by the presence of phospholipases in the venom, even if the phospholipases concerned are not, themselves, myotoxic. The cytotoxins of cobra venom possess no hydrolytic activity of any kind. 

Among several thousand species of sea anemones the toxins of only a few dozen have been investigated. Knowledge of the sea anemone peptides permits them to be categorized as (a) sphingomyelin-inhibitable cytolysins, (b) metridiolysin, and (c) Aiptasia lysin. 

The actions of proteins isolated from sea anemones, or other coelenterates, involve mechanisms different from those described for saponins. Thus, hemolysins from sea anemone R macrodactylus are capable of forming ion channels directly in membranes (98). The basic protein from S. helianthus also forms channels in black-lipid membranes. These channels are permeable to cations and show rectification (99). This ability of S. helianthus toxin III to form channels depends upon the nature of the host lipid membrane (100). Cytolysin S. helianthus binds to sphingomyelin and this substance may well serve as the binding site in cell membranes (101-106). 

U74006F, 21-[4-(2,6-di-l-pyrrolidinyl-4-pyrimidinyl)-l-piperazinyl]-16a-methylpregna-l,4,9(ll)-tiene-3,20-dione monomethane sulfonate U74500A, 21-[4-(3,6-bis(diethylamino)-2-pyridinyl)-l-piperazinyl]-16a-methylpregna-1,4,9(1 l)-triene-3,20-dione hydrochloride VSMC, vascular smooth muscle cell VVC, v. vulnificus cytolysin... 

Figure 6 Sequence alignment of lantibiotic and nonlantibiotic bacteriocin prepeptides. The residues in red indicate those positions that are fully conserved within that class, and those in blue are highly conserved. For the nonlantibiotic bacteriocins, only the leader sequences are shown. The site of proteolysis is indicated by the arrow. For cytolysin, the additional six residues removed by CylA are indicated in green.

Figure 16 Regulatory mechanism of cytolysin biosynthesis. Cytolysin consists of two different peptide chains, CylLL and CylLs. When animal cells approach an Enterococcus faecalis cell, CyHL specifically binds to the animal cells and CylLs becomes a free form, which is able to trigger the two-component regulatory system of CylR1 and CylR2. Consequently, CylR2 activates the expression of operon encoding cytolysin biosynthesis.

Andrews NW, Portnoy DA Cytolysins from intracellular pathogens. Trends Microbiol 1994 2 ... 

RTX family of bacterial toxins, which are a gronp of cytolysins and cyto-toxins. Hemolysin (HlyA) is often quoted as the model for RTX toxins. See Coote, J.G., Structural and functional relationship among the RTX toxin determinants of Gram-negative bacteria, FEMS Microbiol. Rev. 8, 137-161, 1992. 

Zhu J, Bai XF, Mix E, Link H (1997) Experimental allergic neuritis Cytolysin ruRNA expression is upregulated in lymph node cells during convalescence. J Neuroimmunol 78 108-116. 

Shiver, J.W., Su, L. and Henkart, P.A. (1992). Cytotoxicity with target DNA breakdown by rat basophilic leukaemia cells expressing both cytolysin and granzyme A. Cell 71, 315-322. 

Welch RA (1991) Pore-forming cytolysins of gram-negative bacteria. In Mol Microbiol 5 521 -529. 

The venom gland is found at the base of the forcipules. Venom passes through the ducts of the forcipules and is injected into the bite site. The components of centipede venom have not been completely identified. Known components include 5-hy-droxytryptamine, histamine, lipids, polysaccharides, and enzymes including proteinases and esterases. Toxin S, which is a cardiotoxic protein, has been isolated from the species Scolopendra subspinipes. Cytolysin is found in the North American giant centipede, Scolopendra heros. 

Of the 25 animal phyla, almost half are worms. Thus, it is not at all surprising that some worms contain toxins. The nemertines are a phylum of over 800 known species which resemble flatworms but are active predators on crustaceans and other worms. This phylum is exceptionally toxic among the various worm phyla. The Heteronemertine side possesses peptide toxins which appear to be only defensive, as these animals have no means of injecting a venom. The peptides include neurotoxins, which enhance excitability of nerve membranes, and cytolysins, which permeabilize and destroy cell membranes. Members of the Hoplonemertine class inject a venom into their prey using a mineralized stylet located in their proboscis, which is also used to immobilize the prey. Their toxins are alkaloids similar to nicotine which in minute amounts paralyze crustaceans and annelid worms and primarily activate nicotinic acetylcholine receptors. Another well-known worm toxin is nereistoxin, a disulfide-containing alkaloid which also binds to nicotinic... 

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