Topic 8- L2 - Microbial Pathogenesis

Question 1

Infection:

Answer 1

Invasion of body by a disease-causing organism (can by asymptomatic, can result in different disease – not same thing as disease)

Question 2

Disease:

Answer 2

Damage or injury to host organism (overt symptoms). Some bacteria cause disease without establishing an infection (toxins)

Question 3

Pathogen:

Answer 3

An organism that causes disease. Pathogenesis: Mechanism that leads to disease

Question 4

Virulence:

Answer 4

Similar to pathogenicity, but often used to describe the severity of the disease (“highly virulent”)

Question 5

Opportunistic pathogen:

Answer 5

Typically non-pathogenic organism that becomes pathogen under certain circumstances (e.g. immunocompromised host, access to an open wound)

Question 6

Inflammation –

Answer 6

body’s immune response to infection or injury - important

part of how we clear infections

Question 7

Excessive inflammation can have effects from

Answer 7

mild to life-threatening.

Question 8

Immunocompromised individuals with weakened immune response are

Answer 8

subject to greater risk of infection, more difficulty clearing infections

Question 9

Major steps in infection / microbial diseases

Answer 9

Adherence, colonization, invasion, spread

Question 10

For adherence, microbes target specific cell or tissue types such as

Answer 10

Receptors (e.g glycoprotein or glycolipids) on the surface, providing a foothold for invasion

Question 11

Many types/categorizations of adherence factors:

Answer 11

Pili, fimbriae, adhesins, surface proteins, capsules.

Question 12

Mucous membranes:

Answer 12

Tightly packed epithelial cell layers covered with a mucous layer. Important protective layer

Question 13

Mucous membranes line common body access points

Answer 13

(airways, oral cavity, GI tract) and are common places where infections initiated

Question 14

Invasion:

Answer 14

ability of pathogen to enter host cells and/or tissues. Penetrate beyond where microbes (microbiota) normally reside

Question 15

Colonization:

Answer 15

Expanding population – Planktonic or Biofilm

Question 16

Spread:

Answer 16

Moving beyond site of initial infection. Uncontrolled Systemic spread (via bloodstream) often results in very serious infections/disease

Question 17

An example of an invasion strategy by a pathogen.

Answer 17

S. pyogenes secretes an enzyme called hyaluronidase that degrades hyaluronic acid, a polysaccharide that acts as “cement” to connect some types of host cells. This enzyme can disrupt epithelial layer to facilitate invasion.

Question 18

Virulence factor:

Answer 18

Molecules (typically proteins) produced by a pathogen that contribute to its ability to cause disease

Question 19

Nutrient acquisition:

Answer 19

E.g. siderophores, secreted molecules that capture iron from the environment

Question 20

Immune resistance:

Answer 20

Factors that help pathogen survive immune defenses (e.g. resistance to reactive oxygen species)

Question 21

Immune evasion/disruption:

Answer 21

Factors that hide microbe from immune system or that disrupt function of immune system

Question 22

Extracellular enzymes, protein secretion systems/effectors &
toxins :

Answer 22

damage host cells and/or manipulate host cell biology

Question 23

Many ways that pathogens evade the immune system:

Answer 23

• Hide inside cells (intracellular pathogens)
• Produce a capsule that hides surface antigens (preventing immune detection) & can inhibit uptake and destruction by immune cells
• hide or modify other antigens.
• disrupt immune function/kill immune cells (including toxins, secreted enzymes, secretion systems…)

Question 24

hide or modify other antigens.

E.g.

Answer 24

pathogen associated molecular patterns (PA M P s ) such as LPS detected by immune system – trigger immune response

Question 25

Secreted (or surface) enzymes can promote virulence in different ways:

Answer 25

- Provide free up nutrients - Damage host cells - Inactivate immune cell mechanisms - Disrupt barriers to enable pathogen invasion/spread

Question 26

Examples of secreted enzyme virulence factors that operate by affecting blood clotting. S. aureus secretes

Answer 26

coagulase, which induces clots to prevent immune detection. S. pyogenes secretes streptokinase, which dissolves clots, enabling this pathogen to spread

Question 27

What type of secretion system used by pathogens

Answer 27

Type III secretion systems | T3SS

Question 28

T3SS effectors proteins have very specific targets

Answer 28

(often a specific protein) in host cell. Manipulate host cell biology in their favour

Question 29

Different effectors often have

Answer 29

complementary activities

Question 30

Exotoxins (“toxins”) are secreted

Answer 30

protein toxins. Similar to bacteriocins but target host. Amongst the most important virulence factors. (Not made by all pathogens, other make many)

Question 31

Example of a bacterial toxin: ⍺-toxin from Staphylococcusaureus toxin proteins

Answer 31

polymerize in host cell membrane to form a pore. This can have a range of effects, from cell lysis to signaling changes. This toxin has a major effect on the virulence of S. aureus strains.

Question 32

AB-type toxins has two subunits

Answer 32

- A subunit exerts biological effect | - B subunit(s) bind host cell receptor (usually glycoprotein/glycolipid) to mediate uptake

Question 33

A subunits generally modify or degrade a

Answer 33

specific molecule (or set of very similar molecules) – typically a host cell protein.

Question 34

AB-type toxin example: Botulinum toxin

Answer 34

``` produced by Clostridium botulinum. Rarely infects (adult) humans. However - grows/produces toxin on foods we consume ```

Question 35

Botulinum toxin AB-type toxin. B subunit targets

Answer 35

toxin to motor neurons

Question 36

Botulinum toxin AB-type toxin. A subunit is a

Answer 36

protease that cleaves specific SNARE proteins that are required by these cells to release the neurotransmitter acetylcholine.

Question 37

Absence of acetylcholine | release leads to

Answer 37

muscle paralysis

Question 38

toxoids / toxins

Answer 38

Inactivated toxins as vaccines

Question 39

Because toxins efficiently, manipulate | human biology in targeted way – can also be used to

Answer 39

treat non-bacterial disease

Question 40

Botox (botulinum toxin) best example of toxins used for treatment – used to treat range of diseases like

Answer 40

(migraines, cerebral palsy, painful muscle spasms)…in addition to “bunny lines”

Question 41

Toxins vs. secretion systems

Answer 41

- An important difference between toxins & secretion systems is that toxins can diffuse and spread to distant cells/tissues. - Toxins often (not Secretion system effector proteins always) more potent, lone wolves. Effectors (often) more nuanced, work together.

Question 42

Yersinia pestis(plague)

Answer 42

- Gram-negative Proteobacterium - Primarily a pathogen of rodents. Carried by a disease vector – fleas. Fleas spread disease between rodents. - spread form person to person (via lice)

Question 43

Three forms of plague – all caused by same bacterium:

Answer 43

- Bubonic plague (infection of lymph nodes) - Pneumonic plague (infection of lungs) - Septicemic plague (bloodstream - rare)

Question 44

Yersinia pestis - virulence due to ability to

Answer 44

survive/subvert the immune system. | Access infection site (lymph nodes, lungs, blood) & colonize/grow.

Question 45

Main virulence factors for Yersinia pestis include:

Answer 45

- T3SS injects many different effector proteins into immune cells to inactivate immune functions - An abundant fimbrial protein that acts as a capsule - F1 capsule through to inhibit uptake of Y. pestis by immune system & detection of surface antigens