Staphylococcal a-toxin

Ahnert-Hilger G, Bhakdi S, Gratzl M (1985) Minimal requirements for exocytosis a study using PC12 cell permeabilized with staphylococcal a-toxin. In J Biol Chem 260 12730-12734. 

Palmer M, Weller U, MeBner M et al. (1993) Altered pore-forming properties of proteolytically nicked staphylococcal a-toxin. In J Biol Chem 268 11963-11967. 

FIGU R E 7 A similar set of substrates is tyrosine phosphorylated during activation of either intact taenia coli, cultured VSMC, or staphylococcal a-toxin-permeabilized deal longitudinal smooth muscle. In these experiments, tyrosine.-phosphorylated substrates were detected by immunoblotting with antiphosphotyrosine antibodies and enhanced chemiluminescence technology rather than the less sensitive I-labeled protein A technology used in Fig. 2. Stimulation of guinea pig taenia coli with either 10 jcM carbachol (Carb) or 1.5 mM vanadate (Van) resulted in pronounced tyrosine phosphorylation of at least nine substrates with apparent masses of 42-45, 50, 70, 80-85, 95,100, 110, 116, and 205 kDa. In like fashion, stimulation of canine femoral VSMC with 100 jjlM phenylephrine (PE) resulted in enhanced tyrosine phosphorylation of a similar set of substrates (however, note that qualitative differences were evident with respect to some substrates, such as the one of 205 kDa). Similarly, the same substrates appeared to be tyrosine phosphorylated when permeabilized ileal smooth muscle was contracted with Ca + (pCa 4.5). From Di Salvo et al. (1994), Fig. 5, p. 1438. 

The haemolytic activity of staphylococcal a-toxin was inhibited by the ganglioside (2) (containing a 2-acetamido-2-deoxy-D-glucosyl residue) from... 

As an example of the interaction of a toxin that targets plasma membrane for its toxic action, features of staphylococcal a-toxin are briefly discussed to elaborate the relevant points. Staphylococcal a-toxin is hemolytic toxin that is secreted as a single water soluble 33 kDa protein (Jiang et al., 1991 Walker et al., 1992). 

Staphylococcal a-toxin is a 293 amino acid protein that seems to consist of two domains (N- and C-domains) that are separated by a glycine-rich loop (residues 119-143) (Gray and Kahoe, 1984). The loop is surface accessible in the monomeric form but becomes inaccessible in the hexameric form (Tobkes et al., 1985). The toxin is a P-sheet dominated protein with 5 % a-helix, 57 % P-sheets, 12% P-turns and 28 % random coils (Tobkes et al., 1985). 

Table 1. Secondary structure contents of staphylococcal a-toxin (Tobkes et al., 1985)...

Bhakdi, S, Fussle, R and Tranum-Jensen, J., 1981, Staphylococcal a-toxin oligomerization of hydrophilic monomers to form amphiphilic hexamers through contact with deoxycholate detergent micelles. Proc. Natl Acad. ScL U.S.A. 78 5475-5479. 

Staphylococcal a-hemolysin is another widely studied pore-forming toxin. It is used by infectious bacteria to perforate host animal cells by a mechanism that is distinct from that of gramicidin. Several aspects of the stmcture and function of this heptameric protein complex have been smdied. 

Caution A toxin is a poison produced by a living organism. The middle term of staphylococcal enterotoxin B means a toxin that is produced by microorganisms, such as some staphylococci, and causes gastrointestinal symptoms. 

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. 

Certain cellular processes are specifically influenced by gradients of monovalent ions across the plasma membrane. It appears that stimulation of some such processes are actually counteracted by concomitant flux. Ca -dependent processes in turn may be abrogated when pores are large enough to permit rapid egress of cytoplasmic proteins. Therefore, it is useful to differentiate between three types of pores (a) those that are selectively permissive for monovalent ions (e.g. staphylococcal alpha-toxin) (b) those that are permissive for Ca and small molecules, but not for proteins (e.g. E. coli hemolysin) and (c) large pores that allow passage of macromolecules (e.g. streptolysin O). 

Bhakdi S, Bayley H, Valeva A etal. (1996) Staphylococcal alpha-toxin, streptolysin O, and Escherichia coli hemolysin prototypes of pore forming bacterial cytoly-sins. In Arch Microbiol 165 73-79. 

Staphylococcal food poisoning is one of the most common types of food poisoning in the United States. The true incidence of staphylococcal food poisoning is unknown due to lack of information from victims, misdiagnosis of the illness, and inadequate collection of samples for laboratory analyses. A toxin dose of less than 1.0 pg in contaminated food will produce symptoms of staphylococcal intoxication. This toxin level represents a S. aureus population exceeding 100 000 organisms per gram. 

Sato H, Matsumori Y, Tanabe T, Saito H, Shimizu A, Kawano J (1994) A new type of staphylococcal exfoliative toxin from a Staphylococcus aureus strain isolated from a horse with phlegmon. Infect Immun 62 3780-3785... 

Omoe K, Hu DL, Takahashi-Omoe H, Nakane A, Shinagawa K Comprehensive analysis of classical and newly described staphylococcal superantigenic toxin genes in Staphylococcus aureus isolates. FEMS Microbiol Lett 2005 246 191-198. 

Fig. 4 Equilibrium surface plasmon resonance sensor response to staphylococcal entero-toxin B (SEB) in a solution of BSA in phosphate buffered saline (BSA-PBS). Reference-compensated equilibrium sensor response to different concentrations of SEB in BSA-PBS solution for direct and sandwich detection modes (a-SEB concentration 3 ixg/mL in BSA-PBS) [38]...

Exogenous application of GTP analogues or contractile agonists increased the [Ca +J sensitivity of phosphorylation in smooth muscle permeabilized with staphylococcal oi-toxin (Nishimura et al, 1988 Kitazawaeffl/., 1991a). Exogenous application of either histamine or AIF4 (a nonspecific activator of G proteins) to depolarized intact tissues also increased the [Ca +Ji sensitivity of phosphorylation (Rembold,... 

For the same reason that decontamination is only moderately important after individuals are exposed to a respirable toxin aerosol, medical personnel are probably at only limited risk from secondary aerosols. Because toxins are not volatile, casualties of a toxin attack can, for the most part, be handled safely and moved into closed spaces or buildings, unless they were very heavily exposed. Prudence dictates, however, that patients be handled as if they were chemical casualties or, at a minimum, that they be washed with soap and water. The risk to medical personnel is of greater concern with some agents. Secondary exposure might be a hazard with very potent bacterial protein toxins, such as botulinum toxin or the staphylococcal enterotoxins. (Note Decontamination and isolation of patients or remains could be much more important and difficult after an attack with a bacteria or virus that replicates within the body.)... 

The staphylococcal enterotoxins are a family of superantigen protein toxins produced by strains of Staphylococcus aureus. Staphylococcal enterotoxin B (SEB), a toxin often associated with food poisoning, was weaponized as an incapacitating agent by the United States during in the 1960s. When inhaled as a respirable aerosol, SEB causes fever, severe respiratory distress, headache, and sometimes nausea and vomiting. The mechanism of intoxication is... 

Bhakdi S, Waley I, Husmann M, Valeva A (2005) Staphylococcal alpha-toxin, topics in current genetics. In Schmitt MJ, Schaffrath R (eds) Microbial protein toxins, vol 11. Springer, Berlin, pp 91-110... 

Schlosser G, Kacer P, Kuzma M, Szilagyi Z, Sorrentino A, Manzo C, Pizzano R, Malorni L, Poc-sfalvi G. Coupling immunomagnetic separation on magnetic beads with matrix-assisted laser desorption ionization-time of flight mass spectrometry for detection of Staphylococcal Entero-toxin B. Appl Environ Microbiol. 2007 73(21) 6945-52. doi 10.1128/aem.Ol 136-07. 

De Boer, M.L. and Chow, A.W. 1993. Toxic shock syndrome toxin-1 producing staphylococcus aureus isolates contain the staphylococcal enterotoxin B genetic element but do not express staphylococcal entero-toxin B. J. Infect. Dis. 170 818-827. 

Staphylococci (Table 6). The normal sensitivity is 0.5 pg/ml but can be increased to 0.1 pg/ml by a 5-fold concentration of the staphylococcal culture supernatant fluids. Over the years any strain that produced enough toxin by maximum production methods to be detectable by gel diffusion methods was considered a toxin-producing strain. 

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