T3: Micro-organisms in disease

Question 1

Define virulence.

Answer 1

The capacity to cause the disease but also used to describe the degree to which a micro-organism is able to cause disease.

• Staphylococcus aureus and Streptococcus mutans are both pathogenic
• S. aureus is more virulent than S. mutans, as it causes disease much more readily. It is also to do with the severity of the infection

Question 2

Define infectivity.

Answer 2

Relates to the establishment. The ability for a microorganism to become established in the host this is mediated by the microbial ligands on the surface and host cell surface receptors.

Question 3

Define virulence factor.

Answer 3

Virulence factor is any component of the microorganism which aid its ability to cause infection (infectivity and virulence). This is encoded by virulence genes.

Examples:

• Facilitation of adhesion
• Toxic effects
• Tissue-damage
• Interference with host defence mechanisms
• Facilitation of invasion e.g. flagella
• Modulation of host cytokine responses

Question 4

What is the cycle of infection?

Answer 4

Using the consideration of coronaviruses:

1. Entry - this is colonisation. Encounter is contact with the microbe. The point at which the microbe encounters and enters the host. In terms of coronavirus, this is via breathing in respiratory droplets and touching contaminated surfaces. This leads to entry into the upper respiratory tract.
2. Spread (within the host) Coronaviruses (and all viruses) they spread by taking over host cell machinery. They interact with ligands on the host cell and use machinery to replicate.
3. Evading defences (the immune system) for a new virus, adaptive immune system is less important as we do not have pre-existing defences. The innate immune system will kick in. Pathogens often have mechanism to try and interrupt innate immune system: this includes interruption interferon and cytokine production.
4. Multiply and damage - A lot of the damage is done by the immune system rather than the pathogen. Coronaviruses cause inflammation and can progress to the lower respiratory tract. Damage can leave the lung prone to other infections such as bacterial pneumonia. This is true for a lot of viruses, a lot of the damage is done by subsequent bacterial infections. This can be quite problematic in terms of drivers for antibiotic resistance.
5. Disperse In terms of coronaviruses, coughs and sneezes. Often side effects of respiratory diseases, aid the dispersal of the disease. In terms of diarrhoea, there is greater spread of the infection and so greater spread of the pathogen.

Question 5

How can we interrupt the cycle of infection?

Answer 5

We can interrupt the cycle of infection:

• Hygiene measures
• Reducing interactions
• Prevention of aerosols - This interrupts at the point of encounter and entry
• Treatment - Improves the damage. Steroids for example decrease the overactivity of the immune system and so reduce damage.
• Vaccine - Help the defences of the host.

Question 6

What is the cause of pneumonia?

Answer 6

Caused by a number of organisms:

• Streptococcus pneumoniae - most common
• Staphylococcus aureus
• Haemophilus influenzae

Question 7

What is the cause of gonorrhoea?

Answer 7

Caused by Neisseria gonorrhoeae

Question 8

Describe the cycle of infection with relation to bacterial pneumonia?

Answer 8

1. Encounter is by:
   Inhalation of air-borne droplets containing pathogen and contact with mouth of infected individual.
2. Spread and evasion is through virulence factors such as flagella, capsule, pneumococcal surfaces and IgA protease.
3. Through the use of pneumolysin and other factors which cause direct and indirect damage.
4. Dispersal is by droplet transmission.

Question 9

Describe the cycle of infection with regard to gonorrhoea?

Answer 9

1. Encounter - this is through sexual contact with an infected individual through urethral exudate or vertical transmission. The bacteria uses pilli and fimbriae for movement and adhesion respectively; this is crucial for entry and encounter.
2. Spread and evasion is through virulence factors such as flagella, capsule, pneumococcal surfaces and IgA protease.
3. Through the use of endotoxins and other factors, the bacteria can cause direct and indirect damage.
4. Dispersal - production of urethral discharge leads to dispersal by sexual contact.

Question 10

How does S. pneumoniae use a capsule?

Answer 10

Its is a polysaccharide layer on the outside of cells. Step. pneumoniae is an example of a bacteria with this. It is important in evasion:

• Prevents phagocytosis of pathogen by cells of the immune system as they are not recognised as intruders
• It allows S. pneumoniae to pass through mucus (sugary mucus layer in the lungs).
• Also prevents complement-mediated killing.

Question 11

What is PSPA?

Answer 11

Pneumococcal Surface protein A - It works to prevent complement mediated killing.

Question 12

What is the role of IgA protease?

Answer 12

IgA is a secretory immunoglobulin. It is found in the mucus in the respiratory and urogenital tract. It is secreted in the mucus, binds to pathogens and prevents adhesion. IgA protease is an endopeptidase which digests IgA. It targets the hinge region of the heavy chain and the light chain. It targets the amino acid sequence Pro-Pro-Y-Pro (Y = threonine, serine and alanine). The breakdown products of IgA stick to the outsides of the pathogen. Produced by S. pneumoniae and N. gonorrhoea.

Question 13

What is the incubation period?

Answer 13

Incubation period The time between the infection and the manifestation of clinical features e.g. chicken pox this is 10-21 days. For COVID-19, this is around 14 days.

Question 14

What is the period of infectivity?

Answer 14

Period of infectivity Period during which a transmissible organism may be transmitted to another person. In chickenpox this is 48 hours before the onset of the rash to when the lesions have crusted over.

Question 15

What is the role of pneumolysin?

Answer 15

Pneumolysin - secreted by S. pnuemoniae. Multiple monomers come together and bind to cholesterol to bind cholesterol in host plasma membrane. This forms a pore in the membrane. The host cell then releases internal contents and dies.

Question 16

What is the role of Hyaluronidase and Neuraminidase?

Answer 16

These are enzymes capable of degrading: hyaluronic acid (connective tissue) and neuraminic acid (epithelial tissue). Part of the cement that stick the cells together.

Breakdown can:

• Provide nutrients
• Provide more space for organisms to grow
• Activate immune system

Question 17

How does N. gonorrhoae use endotoxins?

Answer 17

Endotoxin - components of the outer membrane.

A component of the outer-membrane in N. gonorrhoeae

Isn’t actively secreted (it would be called an exotoxin instead!). Only released on cell death/lysis. If you kill the bacteria, it will release the endotoxin which will go on and form damage. Whilst the cells is alive the toxin doesn’t do much damage it is only when the cell dies. It causes uncontrolled activation of immune response:

• Inflammation
• Severe tissue damage
• Multiple organ failure (endotoxic shock, or “sepsis”)

Question 18

What is the impact of infection on the host?

Answer 18

1. Inflammation - this is an cause of damage and so can lead to rubor, calor, dolor tumour and functio laesa.
2. Abscess formation
3. Excessive gist response to endotoxin - a direct effect
4. Toxic effects of the exotoxin
5. Granuloma formation

Question 19

What are the virulence factors of S. pyogenes?

Answer 19

Streptococcus pyogenes

S. pyogenes syndromes:
Erysipelas
Streptococcal sore throat
Scarlet fever
Necrotizing fasciitis

Virulence factors include:

• Hyaluronidase and streptokinase - Break down connective tissue components – facilitate tissue invasion
• Toxic shock syndrome toxin: Superantigen - causes a syndrome very similar to that caused by endotoxin release
• Erythrogenic toxin (phage-encoded) - Causes the rash of scarlet fever
• C5a peptidase - inactivates complement component C5a
• Streptolysins -O and –H - Lyse red and white blood cells and platelets

Question 20

What is the impact of exotoxins on the host?

Answer 20

These are proteins that are produced and secreted. They are often very specific. They have very specific effects on very specific cells e.g. diphtheriae toxin which activates protein toxin 2, prevents protein synthesis and causes the cell to die. Cholerae increase cyclic AMP activity leading to a loss of nutrients from the cell - generally ions. Through osmosis, loss of water leads to characteristic diarrhoea. Tetanus prevents the inhibitory transmission, there is continuous stimulation of the exciting transmitter.

Question 21

What is tetanus?

Answer 21

Clostridium Tetani (obligate anaerobe) - an infection of dirty wounds. The wound can be quite trivial. You can end up getting a shot. It can lead to death by repertory paralysis. The toxin produced - tetanospasmin:

• Produced by germination of spores - it is therefore persistent
• Binds to nerve synapses
• Inhibits release of inhibitor transmitters e.g. GAMA in the CNS

This can lead to the characteristic opisothonos (classic arching due to continually exciting muscles) and risus sardonicus (lock jaw).

Question 22

What are exotoxin-mediated infections?

Answer 22

Other exotoxin-mediated infections:

• Cholera – Vibrio cholerae
• Diphtheria – Corynebacterium diphtheriae
• Clostridium difficile infection – diarrhoea/colitis
• E. coli O157 haemorrhagic colitis (verotoxin)
• Staphylococcal scalded skin syndrome – Staph. Aureus (image 2)
• Whooping cough (pertussis) – Bordetella pertussis
• Scarlet fever – Strep. pyogenes

Question 23

Give an account of the tuberculosis infection.

Answer 23

Mycobacterium tuberculosis

They have a atypical cell wall - contain mycolic acid as well as petidoglycan in the cell wall. Granuloma production accounts for the clinical and radiological features of tuberculosis.

Question 24

Define pathogenicity.

Answer 24

Pathogenicity The capacity of a microorganism to cause infection. This requires:

• Transmissibility
• Establishment in on a host
• Harmful effects - often mediated by the host rather than the pathogen itself
• Persistence

Question 25

What infections are associated with granulomas?

Answer 25

A common pathology associated with granulomas is tuberculosis. Others include mycobacteria, histoplasmosis, cryptococcosis, toxoplasmosis. Parasites can also cause these, and non-pathogenetic material. Radiologically we see nodules, these can come with tissue necrosis - caseous necrosis.