Staph, Strep, Cholera, & TSEs. Actions/Types of Bacterial Toxins Invasins Adhesins Enzymes...

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

Glucuronic acid N-acetyl-glucosamine

S. Pyogenes capsule

Host connective tissue

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 alongBrush border of rabbit villi

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

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.