Lecture 4-Toxins-Staphylococcus 2010

Enzymes 1 β toxin sphingomyelinase c hydrolysis

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Enzymes: 1. Β -toxin (sphingomyelinase C): -hydrolysis membrane phospholipids -cytotoxic to erythrocytes, fibroblasts, macrophages, leukocytes Type II Toxins of Staphylococci
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Enzymes: 2 . Hyaluronidase: -hydrolyses, hyaluronic acid, present in matrix of connective tissue, tissue damage -Important for spreading of bacteria Type II Toxins of Staphylococci
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Hyaluronic Acid/ Hyaluronan Figure 19-38. The repeating disaccharide sequence in hyaluronan. This ubiquitous molecule in vertebrates consists of a single long chain of up to 25,000 sugars. Can by up to 1 μ m long.
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Enzymes: 3 . Exfoliative Toxins: -two forms , ETA and ETB - Thought to be serine protease that hydrolysis cell-to-cell bridges (desmosomes) -major cause of exfoliative dermatitis (Staph Scaled Skin Syndrome) -no bacteria nor leukocytes present in lesions Type II Toxins of Staphylococci
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Desmosomes Schematic of a desmosome. Intermediate filaments are anchored to sites of cell-cell adhesion by desmoplaskin.
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Delta-toxin: -3kDa protein -mechanism unknown but likely to be detergent-like (not Channel) Type II Toxins of Staphylococci
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Channel Forming: Alpha-, Gamma-toxin and P-V (Panton- Valentine) Leukocidin - Protein sequence of all three is different but assemble to form very similar channel -monomer is water soluble, binds to target membrane and assemble to form channel -target cell (erythrocyte, hepatocyte, leukocyte) looses osmotic gradient, cell swelling -major cause for tissue damage (Beta-Hemolysis) Type II Toxins of Staphylococci
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Hemolysis Beta: = hemolytic Alpha: = weakly hemolytic Gamma: = non-hemolytic
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Jayasinghe, L. et al. J. Biol. Chem. 2006;281:2195-2204 Proposed assembly pathway for {alpha}-hemolysin
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Important Enzymes Coagulase: direct conversion of fibrinogen to fibrin or indirect via interaction with plasma factor (coagulase-reacting factor) might help to protect bacteria from phagocytosis Catalase: Converts H2O2 to H2O and O2, important diagnostic feature Penicillinase ( β -lactamase): confers Penicillin resistance targets β -Lactam ring of Penicillin
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