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Staph, Strep, Cholera, & TSEs
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Actions/Types of Bacterial Toxins
• Invasins• Adhesins• Enzymes• Enzyme
Inhibitors/activators• Membrane disruptors
• Protein synthesis inhibitors
• Siderophores• Immunological
disruptors• And more.
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Staphylococcus aureus
Causes:
• Boils/Abscesses• Impetigo• Folliculitis• Scalded Skin Syndrome• Toxic Shock Syndrome
• Endocarditis• Osteomyelitis• Septicemia• Surgical wound
infections• Food poisoning• Pneumonia
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Abscess
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Scalded Skin Syndrome
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Endocarditis
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S. Aureus Toxins
• Alpha Toxin/Hemolysin• Leukocidin• Coagulase• Staphylokinase• Hyaluronidase
• Protein A• Staph Enterotoxins(SE) (A-
G)• Toxic Shock Syndrome
Toxin (TSST)• Exfoliation Toxins
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Leukocidin from CA-MRSA
• Target neutrophils
• Alpha toxin targets monocytes & platelets.
Nature.com
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Transduction of Leukocidin Production
Nature.com
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Superantigen
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Superantigens
• TSST-1 (Toxic Shock Syndrome Toxin)• Staph Enterotoxins A - G• Exfoliation toxin
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Streptococcus pyogenes (Group A)
Causes:
• Erysipelas• Necrotizing fasciitis• Streptococcal TSS• Scarlet fever
• Pharyngitis (strep throat)• Puerperal fever• Rheumatic fever
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b-Hemolysis
S. pyogenes
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Step Throat
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Erysipela
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Necrotizing Fasciitis
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Rheumatic Fever
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Scarlet Fever
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S. Pyogenes Toxins
• M proteins• Hyaluronic acid• Protein F• Streptolysins• Hyaluronidase• Streptokinases
• Streptodornases• Proteases• Streptococcal
pyrogenic exotoxins (Erythrogenic toxin)
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M proteins
• Prevent phagocytosis.• Some resemble heart
muscle proteins.
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Hyaluronic Acid
Glucuronic acid N-acetyl-glucosamine
S. Pyogenes capsule
Host connective tissue
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Recent UN Development Program Report
• 2.6B people lack proper toilets• At least 1B get water from sources polluted
with human or animal feces• $10B estimate to halve the above numbers
• “Beyond Scarcity: Power, Poverty and the Global Water Crisis”
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Cholera
• Vibrio cholerae• Survive in estuaries (high salt) and fresh
water; tolerant of alkalinity• Spore-like state – not culturable, but
infectious• Two known serotypes (other serotypes cause
milder disease)• Grow in small intestine
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Cholera
• Host cells lose chlorides, bicarbonates and water
• 3-5 gallons can be lost per day; massive diarrhea
• Blood becomes viscous• Rehydration is best therapy
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Vibrio cholerae alongBrush border of rabbit villi
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Published by AAAS
D. T. Hung et al., Science 310, 670 -674 (2005)
Virstatin inhibits virulence expression in V. cholerae
Virstatin turns off transcriptionof an exotoxin and a pilus
Exotoxin (Cholera toxin) is an enzyme that elevates cAMP inhost cells – leads to fluid loss(gene is part of prophage)
Pilus is for attachment
Virstatin can inhibit cholera infection in mice
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Unusual Quorum Sensing
• In some strains of V. cholerae, QS works the opposite of expectations.
• High concentration of autoinducer inhibits toxin production!
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Cholera Epidemic in Iraq
• 1217 cases in Northern Iraq from August – December, 2007.
• Sulaymaniya province.• Meeting 27.5% of water demand.
SF Chronicle. 12/10/07.
(16,000?)
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Cholera in Haiti, 2010 – 2011
• 6742 cases as of Nov. 3, 2010• 442 dead as of Nov. 3, 2010
• Brought by foreign peace keepers?• Could now be endemic.
• Update: 285,931/4870 as of April 17th.• 473,649/6631 as of Oct. 14th.– paho.org
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Other Bacterial Toxins
• Shiga toxin.• Botulinum toxin.• Tetanospasmin.• Pertussis toxin.• Diphtheria toxin.• Endotoxin.
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Transmissible Spongiform Encephalopathies (TSEs)
• Caused by prions – clumps of abnormally folded proteins– Prions can “recruit” normal proteins to form
prions• Incubation times are usually many years
following ingestion of infected meat• Destroys brain tissue• Sheep, deer, elk, cows, humans• Prions cannot be destroyed by cooking (they
are already “cooked”)
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Prion Protein Structure
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Prion Formation
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• Chronic wasting disease in deer and elk• Scrapie in sheep• Mad cow disease (bovine spongiform
encephalopathy) in cows
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BSE
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Human TSEs
• Creutzfeldt-Jakob disease (CJD) – Cerebrum, thalamus
• vCJD = thalamus, cerebellum– Possible connection to mad cow disease is feared
• Kuru – primarily in New Guinea (related to practice of eating the dead); cerebellum
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Mad Cow Disease
• Bovine Spongiform Encephalopathy (BSE)• Probably arose from practice of feeding cows
other animals (esp. sheep and then infected cows)
• Huge outbreak in Great Britain in mid 1990s• Found in Canada and U.S. in 2003
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Transmission
• Definitely through consumption of brain tissue• What about other tissues?• Found in blood, urine, and other tissues in
mice and deer (recent studies)
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Other Possible Human Prion Diseases
• Alzheimer’s.• Parkinson’s.• Huntington’s.• Amyotrophic Lateral Sclerosis.