Lecture 7- Infection, Pathogenicity + Virulence- Bacterial Toxins

Question 1

Pathogenicity

Answer 1

The ability of an organism to cause disease

Question 2

Virulence

Answer 2

The relative ability of the pathogen to infect a host + cause disease
-degree of pathogenicity

Question 3

Virulence factors

Answer 3

-molecules
-cellular structures
-regulatory systems that enable microorganisms to cause disease

Question 4

Bacterial toxins

Answer 4

-virulence factor
-protein, peptide/ any other substance produced by bacteria which is highly poisonous for living cells in other organisms

Question 5

Why do bacterium’s harm its host?

Answer 5

Main goal of bacteria cell= multiply
Killing host= kills bacteria = no nutrients
Successful bacteria= obtain nutrients + spread with the least amount of energy and host damage

Host damage=
-facilitate invasion (weakened barriers/ immune responses)
-access/liberate nutrients
-reduce competition from other microbes

Question 6

Host response vs disease

Answer 6

Immune response too weak to be effective= no benefit to the host

Immune response excessive= damaging to the host

Question 7

Extracellular enzymes

Answer 7

Slides 9-10

Question 8

Bacterial toxins

Answer 8

Contribute significantly to bacterial disease
Primary causes of some diseases= anthrax + tetanus
-highly potent
-act away from where they are secreted

Question 9

Bacterial toxins

Answer 9

Endotoxins;
-produced when bacteria die/ phagocytosed
-gram negative bacteria only e.g. endotoxic septic shock

Exotoxins;
-secreted by bacteria
-can travel through the body + have an effect far from the site of infection e.g. botulism, tetanus etc

Question 10

Types of toxins

Answer 10

Endotoxin; a lipopolysaccharide component of the gram - bacteria cell = released during active cellular growth + cell lysis

Exotoxin; group of soluble proteins that are secreted by the bacterium; enter host cells + catalyse the modification of a host cell component

Enterotoxin; a protein exotoxin released by a microorganism that targets the intestines. Involved in diarrhoea + food poisoning

Question 11

Impacts of bacterial toxins

Answer 11

-changes to target cells
-facilitate bacterial spread through tissues
-damages cell membranes
-dampen the host immune system
-inhibit protein synthesis

Question 12

Bacterial cell envelope

Answer 12

2 major categories; gram + and gram -

Gram + = no LPS= no endotoxin
LPS release can cause host immune system to be hyper-activated

Question 13

Immune response to endotoxins

Answer 13

-they have pattern recognition receptors that recognise pathogen specific moieties
-known as pathogen-associated molecular patterns (PAMPs)

Examples;
-flagellin, LPS, DNA, chitin and peptidoglycan

Question 14

Endotoxins- host immune system hyperactivation

Answer 14

Inflammation= increases permeability of tissue to immune cells and promotes healing

Uncontrolled, systemic inflammation + septic shock

Inflammatory response can fail to localise + deal with the pathogen ;
-immune cells become overwhelmed
-bacteria spread to other areas of the body
-large amounts of LPS can enter blood circulation

Question 15

Endotoxins- host immune system hyperactivation

Answer 15

Antibiotics?
-antibiotic therapy can aggravate symptoms of massive gram-negative sepsis
-LPS is released simultaneously from all cells being destroyed

Question 16

Toxoids

Answer 16

-exotoxins = may lose toxicity but retain their antigenic properties

-toxin= inactivated (chemically/heat-treated)= known as toxoid

Question 17

Cytotoxins

Answer 17

Known as= cytolytic forms/ haemolysins
-disrupt cytoplasmic membrane of host cells
-destruction of erythrocytes = haemolysis
-liberate nutrients from the destroyed RBC

Example; pore-forming cytotoxin

Question 18

Superantigens + Streptococcal toxic shock syndrome

Answer 18

Dealt with= slide 23-25

Streptococcal toxic shock syndrome

1.invade body via wounds in the skin + can release cytotoxins;
- cleaves host cell junction proteins
- loosens tight gap junctions
- cytotoxicity destroys cels in deeper layers of the skin

Results in=
- tissue damage and hyper-inflammation
- invades deeper into the body
- necrotising soft tissue infections

2. GAS infections are complicated by superantigens
   - cytokine storm -> sepsis -> organ dysfunction
   - toxic shock syndrome

Question 19

Two subunit AB toxins

Answer 19

A subunit= actual toxin, enzymatically active

5 B-subunits= involved in delivery + attachment to target site
-recognises receptors on eukaryotic cell surface; toxins are specific and can exert its effect at a different site to where the bacterial infection is

Examples; cholera toxin, shiga toxin, tetanus toxin and pertussis toxin

Question 20

AB toxins

Answer 20

-all share the AB5 structure
-interfere with signal transduction
-block release of neurotransmitters + protein synthesis

Examples; slides 29-43 (cholera)
*go over cholera toxin, Botox and tetanus toxin= mode of action slide 34, 40 + 44

Question 21

Summary

Answer 21

Pathogenicity= ability to produce disease
Virulence= disease producing power of an organism, degree of pathogenicity within a group of species

-AB toxins have different effects on the same target protein
-G protein= cholera and pertussis toxins
-AB toxins= range of mechanisms affecting the same system
-motor neurons= tetanus + botulism toxins