Staphylococcus aureus a-toxin

Antihemolytic activity. Water extract of the dried seed, administered to rabbits red blood cells at variable concentrations, was inactive vs Staphylococcus aureus a-toxin-induced hemolysis and produced weak activity vs Vibrio parahaemolyticus-induced hemolysis . ... 

Palmer M, Jursch R, Weller U et at. (1993) Staphylococcus aureus a-toxin. Production of functionally intact, site-specifically modifiable protein by intoduction of cysteine at positions 69, 130, and 186. J. Biol. Chem. 68 119-11962. 

Fussle, R., Bhakdi, S., Sziegoleit, A., Tranum-Jensen, J., Kranz, T. and Wellensiek, H. J. 1981, On the mechanism of membrane damage by Staphylococcus aureus a-toxin. Journal of Cell Biology 91,83-94. 

McEwen, B.F. Arion, W.J. (1985) J. Cell Biol 100, 1922-1929. Permeabilization of rat hepatocytes with Staphylococcus aureus a-toxin. 

For cell permeabilization various methods can be applied. Treatment with L-a-lysophosphatidylcholine (LPC) has proven to be a cheap, easy, and versatile way to perforate cells. If soluble cytoplasmic proteins need to be labeled other reagents generating smaller holes, such as Staphylococcus aureus a-toxin, can be used. If only the plasma membrane needs to be permeabilized the LPC concentration should be adjusted to obtain 95% trypan blue-stainable cells. 

Figure 1. Schematic representation of the steps involved in the binding and membrane pore formation by Staphylococcus aureus a-toxin (adapted from Walker et al., 1992). (1) Monomeric form of water soluble a-toxin consists of a N-terminal domain and a C-terminal domain that are separated by a glycine-rich loop. (2) The toxin binds to membrane in its monomeric form. (3) A non-lytic oligomer is formed consisting of up to six subunits. (4) The subunits then penetrate further to form the lytic pore.

Hildebrand, A., Pohl, M. and Bhakdi, S., 99, Staphylococcus aureus a-toxin, dual mechanism of binding to target cells. J. Biol. Chem. 266 17195-17200. 

Gaskin, D. K., Bohach, G. A., Schlievert, P. M., and Hovde, C. J. (1997). Purification of Staphylococcus aureus /3-toxin Comparison of three isoelectric focusing methods. Protein Express. Purif. 9, 76-82. 

Hildebrand A, Pohl M, Bhakdi S (1991) Staphylococcus aureus alpha-toxin. Dual mechanisms of binding to target cells. In J Biol Chem 266 17195-17200. 

Yamaguchi T, Hayashi T, Takami H, Nakasone K, Ohnishi M, Nakayama K, Yamada S, Komatsuzawa H, Sugar M (2000) Phage conversion of exfoliative toxin A production in Staphylococcus aureus. Mol Microbiol 38 694-705 Yamaguchi T, Hayashi T, Takami H, Ohnishi M, Murata T, Nakayama K, Asakawa K, Ohara M, Komatsuzawa H, Sugai M (2001) Complete nucleotide sequence of a Staphylococcus aureus exfoliative toxin B plasmid and identification of a novel ADP-ribosyltransferase, EDIN-C. Infect Immun 69 7760-7771... 

FIGURE 11-13 Membrane proteins with -barrel structure. Five examples are shown, viewed in the plane of the membrane The first four are from the E. coli outer membrane. FepA (PDB ID 1 FEP), involved in iron uptake, has 22 membrane-spanning /3 strands. OmpLA (derived from PDB ID 1 QD5), a phospholipase, is a 12-stranded /3 barrel that exists as a dimer in the membrane. Maltoporin (derived from PDB ID 1 MAL), a maltose transporter, is a trimer, each monomer constructed of 1 6 /3 strands. TolC (PDB ID 1 EK9), another transporter, has three separate subunits, each contributing four /3 strands in this 12-stranded barrel. The Staphylococcus aureus a-hemolysin toxin (PDB ID 7AHL top view below) is composed of seven identical subunits, each contributing one hairpin-shaped pair of /3 strands to the 14-stranded barrel. 

Studies of single channels formed in lipid bilayers by Staphylococcus aureus alpha toxin showed that fluctuations in the open-channel current are pH-dependent (47). The phenomenon was attributed to conductance noise that arises from reversible ionization of residues in the channel-forming molecule. The pH-dependent spectral density of the noise, shown in Figure 6, is well described by a simple model based on a first-order ionization reaction that permits evaluation of the reaction parameters. This study demonstrates the use of noise analysis to measure the rate constants of rapid and reversible reactions that occur within the lumen of an ion channel. 

Robert J, Tristan A, Cavalie L, Decousser JW, Bes M, Etieime J, Laurent F, Onerba. Panton-valentine leukocidin-positive and toxic shock syndrome toxin 1-positive methicillin-resistant Staphylococcus aureus a French multicenter prospective study in 2008. Antimicrob Agents Chemother. 2011 55(4) 1734-9. doi 10.1128/AAC.01221-10. 

E. coll was also engineered to produce Staphylococcus aureus a-hanolysin (SAH) (Jean et al., 2014), a pore-forming protein/toxin that has been recently found to be naturally secreted in a fully functional form in E. coli and to aggressively kill mammalian cancer cells (Swofford et al., 2014). Microbial synthesized SAH was found to increase necrotic tissue and quickly reduce tumor volume (Jean et al., 2014) by creating pores that disrupt and destroy mammalian cellular membranes, as well as induce cell swelling and lysis (Swofford et al., 2014). 

Another group of toxins that are so far known not to act beyond plasma membrane are staphylococcal enterotoxins and heat shock syndrome toxins produced by Staphylococcus aureus. These toxins act as superantigens (Marrack and Kapler, 1990), and have binding sites for major histocompatibility complex II on macrophage cell membrane as well as for the T-cell antigen receptor. Upon binding with T-cells, these toxins evoke massive release of cytokines which become harmful in such a large amount. 

Small GTPases of the Rho family are ADP-ribosylated (e.g., at Asn4l of RhoA) and inactivated by C3-like toxins from Clostridium botulinum, Clostridium limosum, and Staphylococcus aureus. These proteins have a molecular mass of 23-30 kDa and consist only of the enzyme domain. Specific inhibition of Rho functions (Rho but not Rac or Cdc42 are targets) is the reason why C3 is widely used as a pharmacological tool [2]. 

Langer K, Breuer K, Kapp A, Werfel T Staphylococcus aureus-derived entero-toxins enhance house dust mite-induced patch test reactions in atopic dermatitis. Exp Dermatol 2007 16 124-129. 

S. R. Monday G. A. Bohach, Properties ot Staphylococcus aureus Enterotoxins and Toxic Shock Syndrome Toxin-1. in The Comprehensive Sourcebook of Bacterial Protein Toxins, 2nd ed. J. E. Aiout, J. H. Freer, Eds. Academic Press London, 1999 pp 589-610. 

Staphylococcus aureus is an important human pathogen that causes a variety of clinical manifestations, ranging from benign skin infections to life-threatening infections such as septicemia, endocarditis, osteitis, and toxic shock syndrome. The virulence has been ascribed to a coordinated production of a large set of different toxins,... 

Staphylococcus aureus is known for its ability to produce a variety of toxins and many disease syndromes. One of the most frequently observed diseases is staphylococcal tonsillitis. These bacteria are frequently present on tonsils of healthy carriers. Patients that are affected by tonsillitis swallow staphylococci hidden in tonsil crypts. However, in this case staphylococci do not cause any gastrointestinal symptoms in the host organism, even if they enter the gastrointestinal tract. The barrier of gastric juice and conditions in a small intestine inhibit the outgrowth of staphylococci and toxin production -gastroenteritis is caused solely by a toxin produced outside the host organism. 

De Boer, M.L., Kum, W.W. and Chow, A.W., Staphylococcus aureus isogenic mutant, deficient in toxic shock syndrome toxin-1 but not staphylococcal enterotoxin A production, exhibits attenuated virulence in a tampon-associated vaginal infection model of toxic shock syndrome, Can. J. Microbiol., 45, 250-256,... 

Wieneke, A.A., The detection of enterotoxin and toxic shock syndrome toxin-1 production by strains of Staphylococcus aureus with commercial RPLA kits, Int. J. Food Microbiol., 7, 25-30, 1988. 

Y Ji, A Marra, M Rosenberg, G Woodnutt. Regulated antisense RNA eliminates alpha-toxin virulence in Staphylococcus aureus infection. J Bacteriol 181 6585— 6590, 1999. 

Toxic shock syndrome is a very damaging, often fatal condition caused by toxins from Staphylococcus aureus or Streptococcus pyogenes. First reported in children in 1978, it is manifested by high fever, erythroderma (a skin rash condition), and severe diarrhea.6 Patients may exhibit confusion, hypotension, and tachycardia, and they may go into shock with failure of several organs. Survivors often suffer from skin desquamation (flaky skin). 

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