Pathogens

Question 1

Virulence and virulence properties

Answer 1

Virulence is a measure of pathogenicity - what dose of a pathogen causes disease symptoms/damage

Pathogens are identified by virulence genes carried and expressed

Virulence properties include: invasiveness and toxigenicity

Question 2

Definitions:
Pathogen

Infection

Disease

Opportunistic pathogen

Answer 2

Pathogen: microbial parasites able to cause infection

Infection: situation where microbes are growing in host and causing damage

Disease: damage or injury which impairs host’s function

Opportunistic pathogen: cause disease in absence of normal host resistance (ex. immune suppression or poor microbiome strength)

Question 3

Pathogenicity vs Virulence

Answer 3

Pathogenicity: ability of microbe to inflict damage to host

Virulence: measure of pathogenicity
- depends on number of virulence factors

Question 4

Invasiveness vs. toxigenicity

Answer 4

Invasiveness: ability of microbe to become established in host, overcome host defenses and spread in tissues

Toxigenicity: capacity of microbes to produce toxins damage specific tissues of host

Question 5

Steps to infection

Answer 5

1) Exposure
2) Adherence
3) Invasion
4) Colonization and growth
5) Toxicity or invasiveness (not mutually exclusive)
6) Tissue damage and disease

Question 5

Invasive virulence factors

Answer 5

Adhesins

Capsules

Enzymes that destroy host tissues

Invasins

Type 3 secretion systems and type 4 secretion systems

Question 6

Adhesins as virulence factors

Answer 6

Promote specific attachment to host cell surfaces
- one or a few cell types

1) Fimbriae and pilli polymers used to mediate loose attachment (longer)
- gram neg - pilli
- gram pos - pilli and fimbriae

2) Afimbrial adhesins are not filaments but mediate close attachment (single molecule)

Question 7

Capsule as virulence factor

Answer 7

Prevents pathogen from being destroyed by host immune system (phagocytosis)
- not strictly a virulence factor

Can mediate attachment to host or other bacteria

Often gives bacteria a mucoid appearance

Ex. Streptococcus pneumoniae and Haemophilus influenzae

Question 8

Components of the ECM

Enzymes that target degradation of ECM components as virulence factors

Answer 8

Collagen - protein in connective tissue
- Collagenase degrades

Hyaluronic acid - sticky polysaccharide that holds host cells together
- Hyaluronidase degrades
- Ex. Staphylococci, streptococci, clostridia

Lecithin (phosphatidylcholine) phospholipid
- lecithinase degrades and causes cell lysis including in RBCs

Proteoglycan

Fibronectin

Question 9

Example of pathogen which uses ECM targeted enzymes

Answer 9

Clostridium perfringens

Strict anaerobe which gets into wounds and uses lecithinase, collagenase and hyaluronidase to destroy ECM and lyse cells causing gangrene

Maggots can be used to clean away dead flesh to remove anaerobic environment

Question 10

Hemolysins 2 categories as virulence factor

Answer 10

Enzymes: lecithinase and phospholipase

Pore-forming: cytolysins
- pore formed from toxins causes entry of solutes and fluid follows hemolysis occurs

Cause lysis of RBC and other cell types
- called hemolysins bc blood is used on a plate to detect their presence

Question 11

Invasins as virulence factor

Answer 11

Proteins which allow microbes to enter cells - can be surface or injected proteins
- major virulence factor of intracellular pathogens

Benefits for pathogen: protects from immune system, opens up a source of nutrients

Question 12

Modifications intracellular pathogens make to host cells

Answer 12

Block phagosome maturation

Increase vacuole size

Acquire nutrients

Block detection of intracellular infection and response from defenses

Question 13

Type 3 and Type 4 Secretion Systems as virulence factor

Answer 13

AKA Injectisomes

Type 3: forms channel through bacterial cytoplasmic membrane-periplasm-outermembrane-host cytoplasmic membrane so proteins can be injected directly inside

Type 4: Same as type 3 without needle-like structure - more of a “shotgun” than a “needle”

Function: invasion, blockage of phagosome maturation and control over host cells

Used by gram-negative bacteria

Question 14

Toxins definition

Intoxication

Toxin types

Answer 14

Toxins = extracellular enzymes that cause damage to host tissues via virulence or the host’s own immune system

Intoxications result from the presence of a specific toxin
Ex. food poisoning

Endotoxins: part of the bacterial pathogen
Exotoxins: secreted into the surround area as pathogenic bacteria grows

Question 15

Exotoxins

Answer 15

Are soluble, heat-labile proteins secreted or released when organism is lysed
- highly potent

Highly immunogenic = antibody response inactivates them

Categorized by target: neurotoxin, enterotoxin, nephrotoxin, hepatotoxin, cardiotoxin

Also include AB toxins and ECM degrading enzymes

Question 16

AB toxins

Structure

Example

Answer 16

Modify host cells leading to damage inside the host

Composed on enzymatic subunit A and binding subunit B

Subunit A is secreted inside cell and creates some enzymatic change which leads to damage

Ex. Vibrio cholera AB toxin binds to intestinal cell and causes production of increased cAMP by adenyl cyclase –> solutes move into intestinal lumen causing severe diarrhea
- Vibrio cholera then has a way to exit the body and spread via water ways

Question 17

Endotoxins

Answer 17

Heat stable and cannot be inactivated

Weakly antigenic - no antibodies produced

But effective activator of the immune system: fever, shock, weakness, inflammation, diarrhea and septic shock
- problematic because of immune response NOT bc of toxicity

Ex. Lipid A from LPS in gram-negative bacterial pathogens (E. coli, Salmonella)
- Released during lysis and replication of pathogenic bacteria

Question 18

Vaccines against toxins

Answer 18

Toxins are inactivated and converted to toxoids

Toxoids are antigen but non-toxic –> produce antibody response
Ex. Diphteria toxin vaccine DTaP

Endotoxins CANNOT be inactivated by heat or formaldehyde and cannot be converted to toxoids for vaccine