Lecture 22 - Bacterial toxins Flashcards
(20 cards)
what are toxins?
microbial product/component that injures another cell/organism
what are the 2 classifications of toxins?
- Endotoxin = heat stable lipid A of LPS in G-ve
- Exotoxin = heat labile secreted/released protein
what are the 3 ways exotoxins are named?
- host cell types = cyto, neuro, leuko etc
- species that makes them eg cholera, botulinum
- enzymatic ability eg lecithinase hydrolyses lecithin
define type 1-3 toxins
- bind host surface, act extracellularly
- pore/dmg PM, extracellular action
- 2x polypeptide protein
describe type 1 toxins eg superantigens, s aureus, s pyogenes
- superantigens directly bind MHC-2 and 10-20% T cells = huge cytokines
- S aureus toxic shock syndrome toxin (TSST-1) and enterotoxins A-I
- S pyogenes spe = streptococcal toxic shock syndrome + necrotising fasciitis inflammatory destruction
describe the 2 types of type 2 toxins and give examples of each
- pore forming = bind PM cholesterol and polymerise into pores eg s pyogenes streptolysin O = beta haemolysis
- phospholipase = remove polar PM groups to destabilise and lyse PM eg C perfringens alpha toxin/lecithinase/phospholipase
describe type 3 toxins and the 2 types with examples
- A region = binds and translocates then enzymatic on intracellular target
1. simple AB = chain claved by protease + di-S bond linking eg diphtheria, botulinum, tetanus, exotoxin A
2. compound AB = Bs noncovalently linked to As eg cholera, pertussis, LT, shiga, anthrax
describe corynebacterium diphtheria and the disease diphtheria
- G-ve aerobic club rod
- children resp disease = sore throat, swelling, fever, difficulty breathing, some fatal, pseudomembrane in throat
describe the 4 step process of diphtheria A1B1 toxin (DT) and the overall result
- inhibits protein synthesis + induces leucocytes = necrosis
1. B binds heparin binding epidermal growth factor
2. endocytose whole toxin, acidify to unfold = exposed hydrophobic residues on translocation domain
3. insert into PM = pore for A chain
4. A = ADP ribosyltransferase ribosylates essential factor 2 (EF-2) = inhibits protein synthesis
describe bordetella pertussis and the disease pertussis
- G-ve coccobacillus
- whooping cough, childhood, very contagious, mild to prolonged paroxysmal cough, death from apnea
describe the 3 step process of the pertussis A1B5 toxin (PT) and the overall result
- accelerates mucin secretion + alters water transport
- tracheal cytotoxin + adenylate cyclase = kills ciliated cells and inhibits bacterial removal
1. 5 Bs S2, 3, 4x2, 5 bind surface receptor + endocytosed
2. A S1 = ADP ribosyltransferase inhibits Gi
3. adenylate cyclase = cAMP inhibited by Gi so inhibited Gi = uncontrolled cAMP = uncontrolled ion flow = mucous
describe the structure and 2 step process of the cholera A1B5 toxin (CT)
- B = pent ring binds surface monosialosyl ganglioside (GM1) in intestine
- A = 1+2 by di-S
1. A1 enters and ADP-ribosylates Gs
2. Gs stimulates adenylate cyclase = cAMP but ribosylated = permenant activation
3. Cl- + water efflux thru CFTR in intestinal crypt cells
describe clostridium botulinum and the disease botulism
- G+ve anaerobe, spores
- botulism = intoxication = spores cause disease not bacteria
- colonise infant colon bc immature microbiota
what sort of toxin is BT and briefly describe how botulinum toxin (BT) works and 3 uses of it
- proteolytic A1B1 exotoxin
- blocks acetylcholine = prevents muscle contraction = flaccid paralysis
1. treat cerebral palsy and parkinsons
2. botox
3. reduce transmission in muscle spasms/dystonias
describe clostridium tetani and the disease tetanus
- G+ve anaerobe, spores, soil/faeces into deep wounds
- fatal neurological, spastic paralysis
what sort of toxin is the tetanus toxin (TT) and briefly describe how it works
- proteolytic A1B1 exotoxin
- binds neurons, enters cytosol, prevents relaxation signal = constant acetylcholine
compare and contrast BT and TT
- opposite effects but sequence homology
- both Zn proteases cleaving SNARE proteins used for neurotransmitters - TT cleaves synaptobrevin = no inhibition vs BT cleaves SNAP-25 = too much inhibition
- TT binds CNS receptors vs BT binds PNS
describe the features of endotoxins
- LPS from G-ve OM = cell associated or free forms
- > 100ug vs >1ug for exotoxins
- less specific
- heat stable @ 60C
- localised inflammation and dmg
- systemic fever, dmg, shock, death
describe how endotoxins work
overstimulate immune systemically = cytokines, complements, coagulation, B cell mitogen
list 3 examples of endotoxins
- lipid A
- lipoteichoic acid
- PG from CW eg tracheal cytotoxin (TCT) of B pertussis = reduced ciliary mvmt, more mucous, coughing
