VL17: Toxins Flashcards
What is a toxin?
Compounds that are secreted from bacterial cells
generally cause covalent modifications
poisonous substance produced within living cells or organisms
can be small molecules, peptides, proteins capable of causing disease, through interaction with biological macromolecules like enzymes or cellular receptors
are important viulence factors for pathogenicity or evation of immune response
(Wikipedia)
When are toxins produced?
- constitutive production : sometimes (only when useful)
- usually regulated based on environment
Bacteria sense location: iron, oxygen, temperature, concentration of certain nucleotides and QS (how many bacteria are there?)
Which toxins are produced in response to iron regulation? (3)
-diphteria
-shiga and shiga-like
-hemolysin
-tetanus
toxin
What’s the difference between toxins and effectors?
toxin: secreted compounds, cause covalent modifications
effectors: usually secreted into (eukaryotic) cells (type 3, 4,6 secretion), cause non-covalent modifications
no hard distinction, reality is fuzzy, some effectors work like toxins
What is endotoxin? and its characteristics?
Lipopolysaccharide (LPS
- produced only by gram negative bacteria (e.coli, salmonella, neisseria ect)
- endotoxin is LPS of outer membrane and it is an important componen of their ability to cause disease, often after bacteria are killed
- remain associated with cell wall until disintegration of organism (results from autolysis, ecternal lysis mediated by complement and lysozyme, phagocytic digestion of bacterial cells)
- less potent and specific since they don’t act enzymatically
- at low concentrations stimulates protective response from immune system (fever, activation of immune and inflammatory responses)
- if endotoxin reaches blood -> shock and death
- toxicity associated with lipid component
- immunogenicity associated with polysaccharide components
How does LPS interact with the immune system?
binds to LPS binding protein (LBP) in human serum
is transferred to CD14 on Macrophages, associates with TLR4-> pro-inflammatory cytokines (IL1,6,8, TNF-alpha)
What are exotoxins? how do bacteria get the capability of producing them?
proteins secreted by gram+ and - bacteria
- act ouside bacterial cell
- can be encoded on chromosome, plasmid, phage
- plasmid borne toxins often have prots for secretion on same plasmid
phage: huge variety (10 times more phage than bacteria) you find everything in phage genomes, then it becomes a selection factor
Name 3 exotoxins (that act ouside of the cell) examples + how they function
hyaluronidase: acts as hyluronic acid in connective tissue, facilitates bacterial spreading (streptococci and clostridia)
exfolative toxin: protease separating epidermis from tissue underneath, facilitates bacterial spreading in skin (staphylococus aureus) cause of SSSS (staph. scalded skin syndrome)
collagenase: breaks down collagen (connective tissue) in bone and skin (clostridia)
4 classes of exotoxins + 1 example
CT: cytolytic toxins (hemolysins, alphatoxin, clostridium perfringens, Gas gangrene)
AB: A-B toxins: Spastic paralysis, Tetanus toxin, clostridium tetani)
E= enzymatic virulence factor (Hyaluronidase, dissolves hyaluronic acid in connective tissue, Streptococcus pyogenes)
SA: Superantigen toxin (Exfoliating tocin A and B, Staphylococcus aureus)
Summary of how exotoxins bind to animal cell surfaces (3 types)
Type 1: Cell surface-active
- Superantigens
- Heat-stable enterotoxins
Type 2: Membrane damagin:
-Phospholipases and pore forming toxins, (hymolysin, leucocidins)
Type 3: Intracellular toxins
-Most are AB-toxins consisting of a B part binding to a specific receptor in the recipient cell, and an A part translocated into the cell
What are superantigens? what kind of reaction is caused by it?
- Superantigens bind to external regions of TCR and MHC2
- activates large number of Tcells -> non specific immune response
- release of a lot of cytokines (especially TNF alpha) leads to rashes, fever, multi-organ failure, death
What are heat stable enterotoxins? which class of toxins? what is their target?
Type 1 toxin
secretory peptides produced by enterotoxigenic e.coli (ETEC) and others
target guanylate cyclases (increases cGMP levels -> altering signalling pathways)
heat stable up till 100°C
What are type 2 toxins? how do they function?
Type 2 toxins: Membrane damaging toxins
- exhibit hemolysin or cytolysin activity
- induction of cell lysis need not be primary function, can also modulate host cell signal transduction (at low concentrations)
Explain the 2 categories of type 2 toxins
Type 2 toxins: Membrane-damaging toxins
- Channel-forming toxins
- cholesterol dependent cytolysins
- RTX toxin cytolysins, specific tandemly repeated 9 aa residue sequence in proteins (alpha-hemolysin of e.coli) - Enzymatically active toxins
alpha toxin of clostridium perfingens, phospholipase activity, brakes down membranes, lyses blood cells -> bleeding and tissue destruction
How do cholesterol dependent cytolysisn form pores?
Perfringolysin O by clostridium perfringens (PFO)
binds to cholersterol containing membranes, PFO oligomerized, creates whole in lipid bilayer -> cell death
(gangrene)
type 2 secretion system
