Bacterial pathogenesis I

Question 1

What are the different types of symbiosis?

Answer 1

• Commesalism - normal flora - colonisation
• Mutualism - opportunistic pathogen - asymptomatic carriage
• Parasitism - full pathogen - infection

Question 2

What are the different types of infection?

Answer 2

• Local - surface infection (v.cholera, n.gonorrhoeae)
• Invasive - penetrate barriers and spread; or get into wounds (Shigella, Staph aureus)
• Systemic - via blood/ lymph to other sites (S.typhi, N.meningitidis)

Question 3

What are the stages of an infection?

Answer 3

• Acquisition
• Colonisation - adherence
• Penetration
• Multiplication and spread
• Immune evasion
• Damage
• Transmission - shedding
• Resolution

Question 4

What are 3 things that virulence factors help to achieve?

Answer 4

• Evade host defences
• Promote colonisation and adhesion (to establish infection eg adhesins)
• Promote tissue damage (growth, transmission eg toxins)

Question 5

What are the different types of virulence factors?

Answer 5

• Adherence factors (colonise mucosl sites using pili to adhere)
• Invasion factors (secreted enzymes allowing them to undermine tissue structure and get a small niche)
• Capsules (polysaccharides protect from opsonisation and phagocytosis)
• Endotoxins (LPS on G-ve, cause fever etc)
• Exotoxins (protein toxins/ enzymes secreted)
• Siderophores (iron-binding factors to compete with host for iron eg Hb, transferrin and lactoferrin)

Question 6

How do bacteria attach to host surface?

Answer 6

• bacteria such as n.gonorrhoeae have fimbriae which allow the bacteria to catch and adhere to cells
• Other bacteria such as Strep pyogenes, have M-proteins which act as adhesins

Question 7

What are the functions of toxins in an infection?

Answer 7

• Promote adhesion, survival or spread of bacteria (hyaluronidase, collagenases)
• Damage or destroy cells/ cell membranes (phospholipases, pores)
• Interfere with cell metabolism (cholera, diptheria)
• Affect nerves (neurotoxins - botulin and tetanus)

Question 8

What are the different types of toxins? (classified by site of action)

Answer 8

• Type 1 = at cell membrane, not transported in
• Type 2 = on cell membrane, membrane damage
• Type 3 = IC effect after translocation
• EC = cellular matrix or connective tissue

Question 9

What do type 1 toxins do?

Answer 9

• At cell membrane
• Stimulate signalling proteins - bind to GPCR and dysregulate it, changing the IC [cGMP]. Block Na uptake and promote CL loss = acue watery diarrhoea
• Heat stable - doesnt matter if you cook it, it will survive

Question 10

What are superantigens?

Answer 10

• Allow interaction between MHC and T-cells without the presence of an ag
• Dysregulates T cell based immunity allowing massive proliferation in a non-specific way
• eg s.aureus TSST -> toxic shock syndrome; strep pyogenes -> scarlet fever

Question 11

What do Type II toxins do?

Answer 11

• On cell membrane
• Pore formation, enzymic disruption - haemolysins, PLC
• eg staph aureus a-toxin (makes heptamer pore, damages cellular membrane and disrupts ion transport, lysing cell)

Question 12

What is Clostidium perfringens?

Answer 12

• Gram +ve rod
• Anaerobe
• Spore forming
• Found in soil and human gut
• Virulence factor = a-lecithinases, PLC -> lipid membrane damage
• Kills R/WBCs - if gets into blood, can cause severe haemolysis and death

Question 13

What is necrotising fasciitis?

Answer 13

• Certain strains of strep pyogenes have virulence factors that can cause deep infections
• gets in between skin planes and destroys fascia - immune cells cant get to site
• Have to do surgery as cant get antibiotics to site
• Multiple virulence determinants involved (M-protein adhesins, exotoxins, capsule to block opsonisation, streptoLYSIN and leukocidins.)

Question 14

What do type III toxins do?

Answer 14

• IC action after translocation
• Often enzymes that undergo different effects on their targets
• Lots of different toxins with different targets/actions
• eg target G-proteins stopping cell signalling; target rRNA affecting protein synthesis; or actin affecting cellular dynamics and trafficking

Question 15

What is the molecular structure of AB5 bacterial toxins?

Answer 15

• Multimeric - 5 binding domains with an active site in the middle
• Cell infected by the toxin is determined by the binding specificity on the base of the toxin
• eg Shiga toxin, e.coli LT-1, pertussis toxin

Question 16

What toxins inhibit protein synthesis?

Answer 16

• Shigella - dysentery
• Shiga toxin (AB5) gets taken into the cell via Gb3 and secretes N-glycosidase, cleaves adenosine from 28S rRNA
• Diptheria - A-B type toxin
• Internalised, then active A sub-unit cleaved
• interferes with protein synthesis

Question 17

How does E.colitoxin work?

Answer 17

• Heat stable toxin can act on outside of cell
• Binds to receptor, acting on GC -> Cl- efflux and diarrhoea
• Heat-labile toxin binds to a receptor, injecting its toxin inside. Gs -> PKA -> Cl- efflux -> water loss and diarrhoea

Question 18

How does clostridium tetani work?

Answer 18

• acts on interneurones that control motor neurones
• Endopeptidase protein targets synaptobrevin, a key component of presynaptic vesicles that releases NT
• Interneurones can no longer release GABA and glycine -> unopposed continuous excitation -> spastic paralysis

Question 19

What is floppy baby syndrome?

Answer 19

• Infantile botulism
• g+ve spore forming bacteria, anaerobic
• Produces toxin in food causing flaccid paralysis

Question 20

How does Clostridium botulinum work?

Answer 20

• Blocks release of Ach at NMJ

- Endopeptidase for synaptobrevin

Question 21

What does pertussis infection cause?

Answer 21

• Whooping cough - damaged lungs, retina etc
• Bacteria has lots of toxins, some are ciliastatic (stop clearing of organism so it can adhere)
• Also has its own AC that it injects to dysregulate cellular function