Bacterial strategies for host damage Flashcards
What are bacterial toxins?
Virulence factors that are released or excreted that benefit bacteria by killing macrophages and neutrophils.
They also protect bacteria from phagocytic cells
Have specific modes of action and targets; toxins that kill human cells can release iron or carbon sources, or can be subtle by dampening immune response throguh modulation of signalling pathways for cytokine production
How does LPS modulate cytokine production?
LPS (a type of PAMP) binds to PRR on macrophage, activating a signalling pathway that causes TF NF-kB to enter nucleus, which initiates transcription and secretion of cytokines IL-8, IL-1 and TNFa
What is botulinum (botox)?
Toxin produced by Clostridium botulinum causing botulism, a food borne disease leading to paralysis and respiratory collapse
It has benefits in environmental habitat - may play roles in physiology of bacteria and their viruses , possibly regulation of cellular or phage functions or cell-cell signalling. Impact on human body is merely a byproduct
What are examples of superantigens?
Gram +ve cocci
Staphylococcus aureus
Enterotoxin producing Staphylococci – food poisoning
Livestock common reservoir
What are superantigens (sAG)?
Bypass normal antigen presentation by binding to class II major histocompatibility complex molecules on antigen-presenting cells and to non-specific regions of the T-cell antigen receptor
Activate T cells at orders of magnitude above antigen-specific activation, resulting in massive cytokine release
Excess IL-2 TNFa can damage tissue and lead to sepsis and shock
What are the types of toxin?
Type I - Do not enter the host cell e.g. superantigens (e.g. S. aureus)
Type II - Disrupt eukaryotic cell membranes e.g. phospholipases
Type III - A-B toxins; single-chain peptides with multiple domains, such as the Botulinum NTs
Multi-subunit complexes, such as cholera toxin and anthrax toxins
Act intracellularly; B- region binds to the eukaryotic cell by recognising a receptor
A portion enters the cytoplasm
Examples of Type II toxins
Staphylococcus aureus,
Streptococcus pneumoniae,
Escherichia coli,
Mycobacterium tuberculosis
Streptococcus pyogenes
Streptolysin O and S
Clostridial α-toxin Zinc-dependent phospholipase
What are Type III: A-B toxins?
Simplest type of A-B toxin is synthesized as a single polypeptide, which has one binding (B) and one enzymatic (A) domain
Examples of Type III toxins
Cholera enterotoxin - Ribosylation of G proteins stimulates adenylate cyclase and increases cAMP in cells of the GI tract, causing secretion of water and electrolytes
Diptheria toxin - Ribosylation of elongation factor 2 leads to inhibition of protein synthesis in target cells
Tetanus toxin - Zn++dependent protease that inhibits neurotransmission at inhibitory synapses resulting in spastic paralysis
What are some beneficial uses of bacterial toxins?
Immunotoxins can be used to target cancer cells and viral infections
Can be made into effective vaccines through physical inactivation or protein engineering.
What are Type II: Pore forming toxins?
Membrane disrupting toxins form channels in the membrane
Osmotic pressure of the host cell cytoplasm results in cell lysis
Pore-forming toxins tend to be highly helical in their water-soluble state and form pores in membranes using helices.
Interaction with a cell surface receptor
Membrane insertion is often facilitated by acidic pH
leads to conformational change in the protein’s tertiary structure to an insertion-competent state, followed by membrane penetration.
