Bacterial Toxins Flashcards
Exotoxin
Produced by gram neg and positive bacteria
Proteins, released by the bacteria
Heat labile
AB toxins or cytolytic toxins
Endotoxin
Cell wall components of gram neg bacteria
LPS of outer membrane
Heat stable
AB toxins
A and B subunits
B = binding, A = action
AB and AB5
Targets are specific
Superantigens
Bind TCR and MHC 2 of APC
Ex: TSST1 for S. aureus
Non specific, so they can activate a huge number of T cells and cause a polyclonal response
LPS effects at low concentrations
Fever
Vasodilation
Inflammatory response
LPS effects at high concentration
Fever Vasodilation Disseminated intravascular coagulation Hypotension Shock and death
Clostridium spp
Gram positive
Spore forming
Anaerobic rods
Ubiquitous: soil, sewage, normal flora in GI of animals and humans
4 Clostridium spp and what they cause
tetani: tetanus
botulinum: botulism
perfringens: gangrene, food poisoning
difficle: C diff associated diarrhea
Tetanus
Spastic contraction of muscles
Often associated with puncture wound
Infection remains localized then the toxin is absorbed systematically
2 tetanus toxins
- Tetanolysin: oxygen-labile hemolysin
2. Tetanospasmin: plasmid encoded, heat-labile, AB toxin
Tetanospasmin
Binds to specific sialic acid receptors and glyoproteins of motor neurons
Internalized in endosome
Attache to peripheral nerve endings and travels along to CNS and blocks inhibitory impulse to motor neurons
Inactivates proteins that regulate release of inhibitory transmitters glycine and GABA
Toxin binding is irreversible
Botulinum toxin
AB toxin Human disease caused by types A, B, E, F Binds specific sialic acid receptors and glycoproteins on motor neurons (different ones than tetanospasmin) Stays at the NMJ Blocks release of Ach Leads to acute flaccid paralysis
What does clostridium perfringiens cause?
Gas gangrene
Food poisoning
Enteritis necroticans
Gas gangrene
Significant injury (crush, open fractures)
Contamination with soil containing spores
Leads to tissue necrosis
Infection rapidly progressive
2 Gas gangrene toxins
Alpha: lethal lecithinase that has both phospholipase C and sphingomyelinase activities
Theta (perfringolysin): cholesterol-dependent cytolysins, forming a pore and resulting in cell lysis upon contact with cholesterol in the host’s cell membranes
2 C diff toxins
Toxin A (TcdA) enterotoxin Toxin B (TcdB) cytotoxin Only strains producing B (or A and B) cause disease
E. coli
Gram negative rods
Motile, facultative anaerobe
Normal inhabitant of human and animal digestive tracts
Certain strains cause intestinal/diarrheal disease
Others cause UTIs, neonatal meningitis, septicemia
Enterotoxigenic (ETEC) E. coli
Acquired from contaminated food/water
Watery diarrhea in young children in developing countries
Travellers diarrhea to tropical region
Pathogenesis from intestinal attachement (fimbriae) and elaborate toxins (2 types)
2 ETEC toxins
LT: heat labile, AB5 toxin, similar to cholera toxin, stimulates adenylate cyclase, increases cAMP leading to electrolytes and water excretion in intestinal lumen (watery diarrhea)
ST: heat stabile, STa and STb, activates guanylate cyclase, increases cyclic guanosine monophasphate, increases fluid and electrolyte excretion (watery diarrhea)
Enterohemorrhagic (EHEC) E. coli
Causes hemorrhagic colitis (bloody diarrhea) and may lead to HUS
Acquired from contaminated food: undercooked ground beef, raw milk, unpasteurized apple juice, vegetables
Many serotypes, O157:H7 most common
AB5 toxin
Similar to Shiga toxin
Bind glycolipid receptors (gb3), found in varying degrees in membranes of eukaryotic cells
Shigella spp
Gram negative rod, non motile
Causes diarrheal disease, could be severe
4 species: dysenteriae, boydii, fleneri, sonnei
Human pathogen, no animal reservoir
Spread by fecal oral route, less by contaminated food and water
Bloody diarrhea
Infectious dose 10-100
Vibrio spp
Curved gram negative rods
Highly motle
Facultative anaerobes
Typically found in salt water
Environmental organism and human intestinal pathogen
Infection acquired from contaminated water or food
Severe watery diarrhea, can lead to dehydration and death in untreated patients
3 species of Vibrio
cholerae: cholera
parahaemolyticus: gastroenteritis
vulnificus: cellulitis, septicemia
Cholera toxin
AB5 toxin
Bind ganglioside GM1 receptor on intestinal cells
Increase cAMP, leading to electrolytes and water secretions
Staph aureus
Non-motile, gram positive cocci
Colonizes anterior nares
Causes toxin mediated diseases, skin and soft tissue infections, systemic infections
Staph aureus exfoliative toxins
SSSS: staphlococcal scalded skin syndrome
ETA & ETB: In 5% of strains, either can cause disease
ETA: heat stable, chromosomal
ETB: heat labile, on plasmid
Serine proteases
Disrupt cell-adhesion structures
Toxic shock syndrome toxin-1
Causes TSS
Super antigen
Fever, hypotension, rash, and multi-organ failure
Have to treat with penicillin to get rid of the bacteria, as well as clindamycin and Igs to get rid of the toxin
Staph aureus enterotoxin
Multiple enterotoxins identified Enterotoxin A most commonly associated with food poisoning Heat stable Resistant to gastric enzymes Produced by 30-50% of s. aureus
