Staph, Strep, Cholera, & TSEs

Actions/Types of Bacterial Toxins Invasins Adhesins Enzymes Enzyme Inhibitors/activators Membrane disruptors Protein synthesis inhibitors Siderophores Immunological disruptors And more.

Staphylococcus aureus Causes: Boils/Abscesses Impetigo Folliculitis Scalded Skin Syndrome Toxic Shock Syndrome Endocarditis Osteomyelitis Septicemia Surgical wound infections Food poisoning Pneumonia

Abscess

Scalded Skin Syndrome

Endocarditis

S. Aureus Toxins Alpha Toxin/Hemolysin Leukocidin Coagulase Staphylokinase Hyaluronidase Protein A Staph Enterotoxins(SE) (A-G) Toxic Shock Syndrome Toxin (TSST) Exfoliation Toxins

gsbs.utmb.edu/microbook/ch012.htm

Leukocidin from CA-MRSA Target neutrophils Alpha toxin targets monocytes & platelets. Nature.com

Transduction of Leukocidin Production Nature.com

Superantigen

Superantigens TSST-1 (Toxic Shock Syndrome Toxin) Staph Enterotoxins A - G Exfoliation toxin

Streptococcus pyogenes (Group A) Causes: Erysipelas Necrotizing fasciitis Streptococcal TSS Scarlet fever Pharyngitis (strep throat) Puerperal fever Rheumatic fever

b-Hemolysis S. pyogenes

Step Throat

Erysipela

Necrotizing Fasciitis

Rheumatic Fever

Scarlet Fever

S. Pyogenes Toxins M proteins Hyaluronic acid Protein F Streptolysins Hyaluronidase Streptokinases Streptodornases Proteases Streptococcal pyrogenic exotoxins (Erythrogenic toxin)

M proteins Prevent phagocytosis. Some resemble heart muscle proteins.

Hyaluronic Acid S. Pyogenes capsule Host connective tissue Glucuronic acid N-acetyl-glucosamine

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”

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

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

Vibrio cholerae along Brush border of rabbit villi

Virstatin turns off transcription of an exotoxin and a pilus Virstatin inhibits virulence expression in V. cholerae Virstatin turns off transcription of an exotoxin and a pilus Exotoxin (Cholera toxin) is an enzyme that elevates cAMP in host cells – leads to fluid loss (gene is part of prophage) Pilus is for attachment Virstatin can inhibit cholera infection in mice D. T. Hung et al., Science 310, 670 -674 (2005) Published by AAAS

Unusual Quorum Sensing In some strains of V. cholerae, QS works the opposite of expectations. High concentration of autoinducer inhibits toxin production!

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?)

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

Other Bacterial Toxins Shiga toxin. Botulinum toxin. Tetanospasmin. Pertussis toxin. Diphtheria toxin. Endotoxin.

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”)

Prion Protein Structure

Prion Formation

Chronic wasting disease in deer and elk Scrapie in sheep Mad cow disease (bovine spongiform encephalopathy) in cows

BSE

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

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

Transmission Definitely through consumption of brain tissue What about other tissues? Found in blood, urine, and other tissues in mice and deer (recent studies)

Other Possible Human Prion Diseases Alzheimer’s. Parkinson’s. Huntington’s. Amyotrophic Lateral Sclerosis.