Lecture 6 Flashcards
(19 cards)
What are invasins and list the key ones
Definition: Invasins are extracellular proteins (enzymes) secreted by certain bacteria that help them invade host tissues by breaking down host cells or the materials between them.
Many invasins are only produced when bacterial numbers are high enough. (QS)
Key Invasins:
Hyaluronidase
Neuraminidase
Streptokinase / Staphylokinase
Collagenase
Coagulase
Key invasins: Hyaluronidase
Produced by: Streptococci, staphylococci, clostridia
Action: Breaks down hyaluronic acid, a key component in the “cement” holding cells together in connective tissues.
Result: Allows bacteria to spread through tissues; some bacteria can also use hyaluronic acid as a carbon source.
Key invasins: Neuraminidase
Produced by: Vibrio cholerae, Shigella dysenteriae
Action: Breaks down neuraminic acid (also called sialic acid), which helps hold epithelial cells together in the gut.
Result: Disrupts intestinal barriers, aiding bacterial penetration and infection.
Key invasins: Streptokinase / Staphylokinase
Produced by: Streptococci / Staphylococci
Action: Converts plasminogen (inactive) to plasmin (active), which dissolves fibrin clots.
Result: Bacteria can move freely by avoiding clot formation.
Medical use: These enzymes are also used as inexpensive medications to dissolve blood clots in heart attack patients.
Key invasins: Callagenase
Produced by: Clostridium histolyticum, C. perfringens
Action: Degrades collagen, a structural protein in muscle.
Result: Facilitates tissue destruction and causes gas gangrene, a severe infection.
Key invasins: Coagulase
Produced by: Staphylococcus aureus
Action: Causes clotting (opposite of kinases) by interacting with fibrinogen to produce fibrin clots.
Result: Walls off the bacteria from the immune system, helping it stay localised.
Bonus: Binds to collagen through specific adhesins.
Two major types of bacterial toxins
Endotoxins
Exotoxins
Endotoxins
Source: Gram-negative bacteria only
Molecule: Lipopolysaccharide (LPS), found in the outer membrane
Not QS-controlled
Released: When bacteria die (lyse)
Endotoxins structure
Polysaccharide (O-antigen + Core) – Water-soluble, immunogenic
Lipid A – Toxic part; anchored in membrane
Endotoxins effects
Triggers host immune response, which causes harm:
Activates immune cells to release pyrogens (fever-causing proteins)
Causes fever, vomiting, diarrhoea, inflammation, coagulation
Can lead to shock, but usually not fatal
Endotoxins lethality and pharmaceutical issues
LD₅₀ (lethal dose for 50% of test subjects): 200–400 µg
Compared to:
Botulinum toxin: LD₅₀ = 25 picograms = 0.000025 µg!
Pharmaceutical Issues:
Can contaminate drugs/equipment:
Limulus amoebocyte lysate (LAL) assay: Test for endotoxin contamination using horseshoe crab blood
Removal: Heat at 250°C for 30 min, or filter sterilisation
Regulation: < 25 pg/mL (0.25 EU)
Exotoxins and list main ones
Source: Mostly Gram-positive, some Gram-negative
Actively secreted proteins
Highly specific targets
Much more potent than endotoxins
Often QS-controlled
Main:
Cytotoxins
A-B toxins
Botulinum neurotoxin
Exotoxins: Cytolytic Toxins (Cytotoxins)
Mechanism:
Insert into host cell membranes, forming pores
Enzymatically degrade membrane phospholipids
Haemolysins: Lyse red blood cells (RBCs) – but can affect other cells
Leukocidins: Target immune cells (white blood cells)
Examples:
α-toxin (Staphylococcus) – pore-forming
Exotoxins: A-B toxins
Structure:
A = Active (toxic) subunit
B = Binding subunit (recognises host cell surface)
Function:
B binds to specific glycans on host cell
Conformational change → forms a pore
A enters cytosol, disrupts normal function (e.g., protein synthesis)
Exotoxins: Botulinum Neurotoxin
Produced by: Clostridium botulinum (Gram-positive)
Mechanism:
Binds to presynaptic motor neuron terminals
Blocks neurotransmitter (acetylcholine) release
Causes flaccid paralysis, then death
Forms: 7 types (A–G)
Most toxic natural substance known
Inhalation of 0.8 µg is fatal in humans
Medical use: Botox® – smooths wrinkles by paralysing muscles
Superantigens
Definition: Proteins that cause a massive immune response
Mechanism:
Bind outside the normal antigen-binding site on T-cell receptors (TCRs)
Stimulate 5–25% of all T-cells (vs. normal 0.05%)
Leads to cytokine storm
Can cause shock, fever, inflammation, organ failure
e.g Staphylococcus aureus: Toxic Shock Syndrome Toxin 1 (TSST-1
Toxin Exposure Types: Intoxication
Toxin is ingested directly (pre-formed)
Examples:
Staph. enterotoxins (A–D): superantigens
C. botulinum toxin: A-B exotoxin
Toxin exposure types: Colonisation
Pathogen grows in host → produces toxins inside body
Requires high density (biofilm formation)
Toxin production is QS-controlled
Examples:
Salmonella, E. coli: A-B enterotoxins
Siderophores – Iron Scavengers
Problem: Both humans and bacteria need iron to grow
Host defence: Humans bind iron tightly using:
Haemoglobin
Transferrin (in blood)
Lactoferrin (in secretions)
Bacterial strategy: When iron is scarce, bacteria produce siderophores
Small, high-affinity molecules that steal iron from transferrin/lactoferrin
Bacteria have receptors to take up Fe-siderophore complexes
