Bacterial Pathogenicity

Question 1

Define pathogen

Answer 1

• Pathogen: microorganism that is able to produce disease

Question 2

Define pathogenicity

Answer 2

• Pathogenicity: ability of microorganism to cause disease

Question 3

Define virulence

Answer 3

• Virulence: degree of pathogenicity

Question 4

Define opportunistic pathogen

Answer 4

• Opportunistic pathogens: bacteria that do not need to cause disease to enable transmission

Question 5

Define obligate pathogen

Answer 5

• Obligate pathogens: require a host for survival and transmission. Usually cause disease

Question 6

Define virulence factors

Answer 6

• Virulence factors: mechanisms to avoid host defences and multiply

Question 7

What are 3 categories of factors that enable disease in a host + examples within each category

Answer 7

Pathogen factors
* Virulence
* Enviro stability
* Route of entry
* Infective dose
* Tropism
* Susceptibility to host defence
Host factors
* Species
* Breed
* Age
* Sex
* Genetics
* Physiologic
* Immune status
Modifying factors
* Stress
* Enviro
* Poor nutrition
* Tissue damage
* Immunosuppression
* Metabolic dysfunction
* concurrent disease

Question 8

List 5 types of host defences used

Answer 8

• Peristalsis/ciliary movement will clear
• Commensal microbiota
• Glycoproteins
• Mucus: lysozyme/peptides/Ig/complement
• Tight junctions of epithelium

Question 9

What are the 2 mechanisms of pathogenicity

Answer 9

invasiveness

toxogenesis

Question 10

Define invasiveness

Answer 10

Invasiveness: ability two invade tissue
* Mechanisms for colonization: adhesins/invasins
* Ability to overcome host defence

Question 11

Define toxogenesis

Answer 11

Toxogenesis: ability to make toxins

Question 12

Define endotoxin

Answer 12

• Endotoxin: bacterial cell-associated substance
  o Transported by blood/lymph
  o Cytotoxic to cells away from original point of invasion/growth
  o Mainly from gram (-)
  o From cell wall (lipid A/LPS) – released when cells die and wall breaks
  o Causes nonspecific signs related to inflam:
   Fever/WBC change/DIC/hypotension/shock/death

Question 13

Define exotoxin

Answer 13

• Exotoxin: make from bacterial cells and act at tissue sites away from bacteria
  o Mainly from gram (+)
  o Enzymes and proteins that are secreted - with specific target
  o Heat sensitive
  o High biological activity

Question 14

Provide 2 examples of exotoxin related disease

Answer 14

Pyoderma in Dogs: Staphylococcus pseudointermedius exfoliating toxin
* Exotoxin: specific toxin targeting specific receptor

Enterotoxigenic enteritis: E. coli enterotoxins causing scours
* Toxin activated ion/water pump = osmotic diarrhea
* Colonize microvilli of small intestines
* Causes functional lesion – no structural lesions

Question 15

What are superantigens

Answer 15

• Pyrogenic exotoxins made by S. aureus and S. pyogenes = superantigens
  o Directly bind T cells/APC

Question 16

What are the steps of pathogenesis

Answer 16

Establish Infection/Colonization

Evade Host Defences

Question 17

List the 4 portals of entry for bacteria

Answer 17

Portals of Entry: urogenital/GI/resp/conjunctiva

Question 18

What is the mechanism of colonization? Define the different parts.

Answer 18

• Receptor; carbohydrate or peptide residue on eukaryotic cell
• Bacterial ligand: adhesin (macromolecular component of bacterial cell surface)
  o Ex. fimbriae

adhere to eukaryotic cell/tissue (need receptor/ligand)

Question 19

What are 3 factors that adherance depends on?

Answer 19

• Tissue tropism
• Species specificity: infect certain species
  o Enteropathogenic E. Coli K88 in pigs only
• Age specificity

Question 20

What is tissue tropism

Answer 20

• Tissue tropism: preference for tissue

Question 21

What is the counter attack complex? Provide an example

Answer 21

Counter attack: understanding virulence mechanisms can help prevent disease
* Ex. Pigs have receptor for F4 E. coli K88 fimbrae > breed them to not have the receptor or use vaccine to make anti-F4 (fimbrae) Ig

Question 22

What virulence factor allows bacteria to enter

Answer 22

• Invasins: factors that allow internalization of bacteria

Question 23

What is the type 3 secretion system? give an example

Answer 23

• Type 3 secretion systems
  o Many gram (-) have: deliver effector proteins
  o Hijack host cell signalling
  o Secretion (into ECF) or translocation (directly into host)
  o Ex. Salmonella typhimurium: deliver effectors/invasins that change host actin = increases uptake in membrane vacuoles
   Effector protein SopB induces enterocytes = induce transformation into M cells = increase colonization and invasion

Question 24

What are spreading factors

Answer 24

• Spreading factors: bacterial enzymes that impact physical properties of tissue matrices/intracellular spaces = increase pathogen spread

Question 25

List 4 types of spreading factors. What do they do? Which types of bacteria use them?

Answer 25

o Hyaluronidase: attack intracellular matrix/connective tissue (form encapsulations in matrix)  Made by streptococcus/staphylococcus/clostridia o Collagenase: break collagen in muscles (facilitate gas gangrene)  Made by clostridium histolyticum and perfringens o Neuraminidase: degrade neuraminic acid (aka sialic acid)  Form residue in intestinal mucus  Made by vibrio cholerae and shigella dysenteriae o Streptokinase/Staphylokinase: kinase enzymes convert plasminogen to plasmin (digest fibrin/prevent clotting)  Made by streptococcus and staphylococcus

Question 26

What are the 3 main roles of complement

Answer 26

tag microbes for phagocytosis, microbial lysis (MAC), pro-inflam

Question 27

What are 3 mechanisms of complement evasion? How does it prevent complement

Answer 27

o Capsules: polysaccharide capsule = hide bacterial components  Prevent complement formation o LPS: main complement target for gram (-) = can change attachment of sialic acid resides to LPS 0 antigen  Prevent MAC o Destroy complement: extracellular enzyme (ex. Pseudomonas aeruginosa)

Question 28

What are 4 mechanisms of phagocytosis resistance

Answer 28

o Avoid contact with phagocytes o Prevent engulfment o Prevent lysozyme o Kill/Damage phagocytes

Question 29

How do bacteria avoid phagocytes? Provide examples

Answer 29

 Stay in regions where phagocytes can’t go: lumen of GII/oral cavity/urinary/mammary/kidney tubule  Hide antigenic surface * Staphylococcus aureus: cell bound coagulase (clot fibrin on bacteria surface) * Group A Streptococcus: hyaluronic capsule  Inhibit phagocyte chemotaxis * Mycobacterium tuberculosis

Question 30

How do bacteria prevent phagocytosis engulfment? Provide examples

Answer 30

 Antiphagocytic molecules on surface * S. pneumoniae/Klebsiella pneumoniae: Polysaccharide capsule * Group A streptococcus: M protein/fimbriae * Pseudomonas aeruginosa: Surface slime polysaccharide * E. coli: O antigen associated with LPS (capture heavy chain of Ig in a configuration where phagocytes can’t bind) * S. aureus:Protein A (cell bound/soluble)

Question 31

3 mechanisms bacteria use to survive in phagocyte? Provide examples

Answer 31

 Inhibit phagosome-lysosome fusion * Salmonella/Leigonella/Chlamydiae/Mycobacterium avium paratuberculosis  Surrvivee in phagolysosome * Bacillus anthracis/S. aureus/Coviella burnetii  Escape phagosome * Rickettsia (make phospholipase that lyse phagosome)

Question 32

Explain mechanisms bacteria use to kill phagocyte? Provide examples

Answer 32

 Kill before engulfment  Hemolysin: extracellular enzymes made by gram (+) * Pyogenic cocci (S. pyogenes/S. aureus)  Streptolysin: secrete by pathogenic streptococcus * Streptolysin 0 binds cholesterol in membranes = lysosomal granules in neutrophils explode + release contents into cytoplasm  Kill after ingestion * Mycobacteria/Brucella/Listeria

Question 33

List the mechanisms bacteria use to evade humoral immunity

Answer 33

o Attack: Aggressive/acute attack (no time for Ig prod.)/ proteinase (degrade Ig) o Protect: Cell wall protection: capsule/peptidoglycan/LPS o Hide: Intracellular hiding/antigenic mimicry (campy LPS/strep M protein) o Superantigens: divert cell immune response + make non-neutralizing Ig

Question 34

List 2 mechanisms of host damage due to bacteria. What kind of damage do they do?

Answer 34

Direct bacterial (virulence factors): protease/hemolysin/toxin * Cardiovascular disturbances * Destroy blood vessel * Diarrhea * Disrupt NS and plasma membranes * Inhibit protein synthesis * shock Induce host immunity: ROS/nitrogen species/inflammation/septic shock