BT4-7: Intro to bacterial pathogenesis

Question 1

What are different sources of pathogens ?

Answer 1

Endogenous (comes from the animal itself)
Spread between animals of same species (epizootic)
Spread between animals of different species (zoonotic)

Question 2

What are the different methods of transmission? Define each one

Answer 2

Horizontal transmission: from another animal or environment
Vertical transmission: from parents to offsprings
Direct transmission: through mucosa/droplets
Indirect transmission: faecal-oral, fomites, arthropods, iatrogenic/nosocomial

Question 3

What affects the areas of entry of the pathogen?

Answer 3

Its mode of transmission

Question 4

What are the different areas of entry of pathogens?

Answer 4

If pathogen is inhaled, it will enter by the respiratory tract.
If pathogen is ingested, it will enter by the GI tract.
If pathogen is sexually transmitted, it will enter by the urogenital tract.

Question 5

Define infective dose.

Answer 5

The amount of bacteria required to establish an infection.

Question 6

What affects the establishment of pathogen?

Answer 6

Motility (not always required) & chemotactic ability & adherence

Question 7

What are the different mechanisms of motility of a bacteria?

Answer 7

Flagella
Endoflagella
Recruiting host’s actin filaments for motility.

Question 8

What is special about endoflagella?

Answer 8

They are found between inner & outer membranes of the bacteria, so they are hidden & are not detected by the host immune system, but are still very effective at conferring mobility.

Question 9

What confers adherence to bacteria?

Answer 9

Adhesins

Question 10

What are the different types of adhesins?

Answer 10

Fimbriae in gram negative bacteria
Non-fimbrial adhesins in gram positive bacteria

Question 11

How do adhesins work?

Answer 11

They bind to glycoprotein in the ECM/on cell surface

Question 12

How do bacteria invade host cells?

Answer 12

They use invasins & proteases.
Invasins remodel the host’s cytoskeleton to allow the bacteria to enter.
Proteases disrupt tight junctions which allows the bacteria to enter.

Question 13

How does rapid replication overcome host defences?

Answer 13

It can overwhelm the host immune system.

Question 14

What does low antigenicity mean?

Answer 14

It means that the pathogen’s antigens are not well-recognised & there is no immune response produced against it.

Question 15

What are examples of bacteria with low antigenicity?

Answer 15

Pasteurella multocida has a hyaluronan capsule. Hyaluronan is found in ECM of host & therefore it “hides” the bacteria.
S. aureus has hyaluronidase which allows it to break hyaluronan & move on to the next stage.
E. coli has a sialic acid capsule that resembles host molecules.

Question 16

What is tolerance in bacteriology and how does it occur?

Answer 16

Tolerance is when the host immune’s system is no longer sensitive to a bacteria’s antigens. It usually occurs via vertical transmission or if the bacteria has so much antigens that it desensitises the host to them.

Question 17

Give examples of bacteria that overcome host defences by inducing tolerance

Answer 17

Chlamydia spp. is often transmitted vertically so the host’s immune system does not recognise it as foreign & tolerates it.
Vibrio cholera produces a lot of antigens so the host is no longer sensitive to them.

Question 18

How do bacteria prevent phagocytosis?

Answer 18

Prevent opsonisation
Produce leukocidins
Produce anti-inflammatory cytokines to prevent inflammation
Inhibit chemotaxis
Inhibit apoptosis of host cells
Prevent phagosome-lysosome fusion

Question 19

Give examples of bacteria that prevent opsonisation & how they do it.

Answer 19

Salmonella has features on its LPS that block the activation of complement.
Mycoplasma spp. & Streptococcus spp. have IgA proteases.
S. aureus produces staphylokinase that activates plasminogen to plasmin which degrades IgG & complement.
Pseudomonas aeruginosa produces extracellular enzymes that inactivate complement.

Question 20

Which bacteria is able to survive intracellularly without being killed?

Answer 20

Rickettsia, Mycobacterium

Question 21

How do bacteria hide from the host immune response?

Answer 21

They can coat themselves in host molecules.
They stay in immune-privileged sites or key body areas.
They show antigenic variation so it’s harder for the immune system to recognise them.

Question 22

How do bacteria show antigenic variation?

Answer 22

Antigenic drift which occurs by mutations
Phase variation which occurs by switching on/off a gene involved in antigens.

Question 23

Give examples of extracellular products that help bacteria evade host’s immune responses.

Answer 23

Streptolysin O, an extracellular toxin that damages phagocytes.
Staphylococcal teichoic acid, an extracellular antigen that binds to opsonins.

Question 24

What nutrient is key to bacterial proliferation?

Answer 24

Iron

Question 25

What kind of damage can bacteria cause to host cells?

Answer 25

Direct damage like : cytolytic damage, enzymatic damage & damage to signalling/apoptotic pathways. Indirect damage is the immunopathology like : inflammation, antibodies, hypersensitivity reactions.

Question 26

Define endotoxins.

Answer 26

Toxins that are part of the bacteria.

Question 27

Define exotoxins.

Answer 27

Toxins that are secreted out of the bacteria.

Question 28

Give examples of exotoxins of bacteria & what they do.

Answer 28

Alpha toxin of C. perfringens that target phospholipase C & result in membrane damage. Alpha toxin of S. aureus that form pores in the membrane. E. coli has toxins that hyperactive adenylate cyclase & overproduces cAMP which leads to osmotic imbalances. E. coli has verotoxins & Shiga-like toxins that bind to Gb3 & inhibit protein synthesis. C. diphtheriae has toxins that form a pore in the cell membrane & inactivate protein synthesis. C. tetani prevents the release of inhibitory neurotransmitters which leads to permanent stimulation of synapse.

Question 29

Give examples of endotoxins of bacteria.

Answer 29

Lipid A of LPS

Question 30

How do superantigens cause cell damage?

Answer 30

Superantigens activate T cells through MHC II but they bind outside the peptide groove so they dysregulate T cells.

Question 31

What are the outcomes of bacterial infections?

Answer 31

Complete recovery Recovery with persistent damage Persistance & carriage Death

Question 32

What affects the outcome of bacterial infections?

Answer 32

Host factors: immune status, genetic susceptibility, if the host has a co-infection or if the host has been exposed to this pathogen before. Bacteria factors: virulence Environmental factors: stocking density, climate, hygiene.