Determinants of disease Flashcards
Virulence factors
adhesion invasion evasion of host defense obtaining nutrients from host toxicity
Measuring virulence
ID50- dose to infect 50% of hosts
LD50- dose to kill 50% of hosts
Types of transmission
Direct-host to host transmission (eg respiratory, body contact, faecal-oral, body fluids, vertical transmission)
Indirect- host to host through living or inanimate objects (eg soil, contaminated water/food, fomites)
Portals of entry
Skin- though not if it’s healthy
Mucousal barrier-warm, moist, every bacterium’s wet dream!
Bacterial adhesins
Proteins: fimbrial, afimbrial surface proteins
Polysaccharides: capsule compenents, techoic/lipotechoic acid
Extracellular invasion
Gets to niches in tissue that aid in proliferation and spreading
Produces enzymes that: attacks extracellular matrix, degrades carb/protein complexes and disrupt cell surface
Intracellular invasion
Rickettsia spp and mycobacteria leprae are obligate intracellular
Phagocytic cells invaded through phagocytosis, while non phagocytic cells are induced into doing phagocytosis
Phagocytosis
- Bacterium binds to cell surface of phagocyte
- Cytoskeleton pushes membrane around bacterium creating large vesicle
- Phagosome moves into cytoplasm
- Phagosome fuses with lysosome forming a phagolysosome
- Bacterium gets rekt and digested
Surviving phagocytosis
Stay in phagolysome
Prevent formation of phagolysosome (salmonella)
Destroy/escape phagosome and live in cytosol
Invading non-phagocytic cells
- Bacterial proteins recruit host proteins to induce phagocytosis
- Secretion system used by g-ve bacteria (salmonella, psuedemonas)
- Invasion proteins injected
- Activate host signalling and recruit actin
Biofilms
Attach to surface and become enveloped in matrix
Protects from phagocytosis, antibiotics, disinfectants
High bacterial density produces virulence factors through quorum sensing
Nutrition
Limiting nutrient is iron contained in transferrin, lactorferrin, ferritin, haemoglobin
Uptake using cell surface proteins TBP (Transferrin) and HBP (haemoglobin)
Or by secreting small compound with very high affinity for iron to capture iron from host proteins or insoluble ferric salts
Siderophores
Produced when iron concentration is low
Has a low molecular weight and competes for both free and bound iron
Transports iron into cell
Enterobactin is an example of a siderophore
Evading complement
Capsule around cell- thick polysaccharide layer to prevent complement activation
LPS O antigen has extended O chains prevent complement activation
Resisting phagocytes
Prevent contact with phagocytes
Affect phagocyte migration- S.pyogenes peptidase cleaves complement factor C5a
Destroy phagocytes- using leukocidins
Evade host-antibody response
Bind host proteins so its not seen as foreign- M protein S.pyogenes
Use surface protein to make antibodies bind backwards- Protein A by S.aureus and Protein G S. Pyogenes to prevent opsonisation
Toxin damage
Cause host damage and induce inflammation
Exotoxin: Toxins secreted during growth
Endotoxin: Toxins released on lysis
Types of exotoxin tranmission
Ingestion of preformed exotoxin- food poisoning
Tissue is infected and then exotoxin release occurs
Exotoxins
Usually proteins therefore heat labile
Host site specific exotoxins
Usually AB toxins: A is the toxin, B is for targetting
Membrane disrupting toxins
Pore forming toxin- Exotoxin forms pore in membrane and uncontrolled entry of water occurs causing lysis
Bilayer disruption- Phospholipase exotoxin cause disruption of bilayer leading to lysis
Superantigen
Produced by staphylococci and streptococci
Staph produces TSST, Strept produces 6 pyrogenic toxin
Causes a massive non specific inflammatory response
Leads to endothelial damage, circulatory shock and multi organ failure
Lipid A component of LPS
Heat stable and in the outermembrane of g-ve bacteria
Released when bacteria die inducing fever, complement activation, clotting cascades and toxic shock
Regulation by numbers: quorum sensing
Many microbes only produce virulence factors until a quorum (min no of cells) is reached
Quorum sensing
Autoinducer (AI)- small diffusable molecule
R protein- activates gene transcription when it binds to AI at high concentrations of AI
High Ai concentrations only occur at high cell densities
