Molecular Basis of Bacterial Virulence

Question 1

What are virulence factors?

Answer 1

Molecules produced by pathogens that contribute to the pathogenicity of the organism, e.g: toxins

Question 2

Describe the pathway of pathogens

Answer 2

Reservoir of pathogens comes into contact with the host and they:
Adhere/colonise and invade
Evade host defences
Multiply/complete their life cycle
Exit the host (damaged)

Pathogens can spread back to the reservoir or to another host

Question 3

Definition of virulence?

Answer 3

Capacity of a microbe to cause damage to the host; result of variation in genes

Question 4

5 examples of virulence factors?

Answer 4

Adhesin - enable binding of the organism to host tissue

Invasin - enables the organism to invade a host
cell/tissue

Impedin - enables the organism to avoid host defense mechanisms

Aggressin - causes damage to the host directly

Modulin - induces damage to the host indirectly

Question 5

3 types of Staph. aureus virulence factors?

Answer 5

Fibrinogen Binding Protein (an adhesin)

Leukocidin (PVL - specific toxicity and killing for leukocytes)

TSST-1 is a toxin (shock, rash, desquamation)

Question 6

Locations of S. aureus?

Answer 6

Anterior nares and perineum

In the environment, it can be acquired from the community of nosocomial (hospital)

Question 7

Describe nosocomial infection with Staph. epidermidis

Answer 7

Associated with foreign devices, e.g:c catheters

Question 8

Pathogenicity of Staph. aureus with relation to its variable presentations?

Answer 8

Superficial lesions can range from boils to abscesses

Systemic presentations can be life-threatening

Toxinoses (toxic shock and scalded skin syndrome)

Question 9

6 presentations of Staph. aureus as a skin infection?

Answer 9

Rash
Folliculitis
Abscess
Carbuncle (multilocaular abscess)
Impetigo
Scalded Skin Syndrome

Question 10

Function of adhesins?

Answer 10

Extracellular matrix molecules that are present on epithelial and endothelial surfaces as well as a component of blood clots

Question 11

Examples of adhesins and genes?

Answer 11

Fibrinogen-Binding (ClfA ClfB)

Collagen binding (CNA)

Question 12

Examples of how pathogens evade host defences?

Answer 12

Protein A binds the Fc domain of IgG

Also, α-toxin is a membrane disrupting toxin that creates pores, causing haemolysis and tissue damage

PVL (Panton-Valentine Leukocidin) is a cytotoxin (β-forming toxin) assoc. with increased virulence of certain strains of Staph. aureus

Question 13

Definition of toxinosis?

Answer 13

Any disease caused by the action of a toxin, for example:
TSST-1 (Toxic Shock Syndrome Toxin - 1)
Staphylococcal food poisoning
Scalded Skin Syndrome

Question 14

Symptoms of TSST-1?

Answer 14

Rapid progression (48 hrs) with high fever, vomiting, diarrhoea, sore throat, muscle pain

Question 15

Symptoms of Staph. food poisoning?

Answer 15

Intoxication, vomiting and diarrhoea that are self-limiting (1-5 hrs)

Question 16

Symptoms of Scalded Skin Syndrome?

Answer 16

Exfoliatin toxins (ETA and ETB) are released by Staph. aureus and tager Desmoglein-1

This often affects neonates, (face, axilla and groin); there is red, blistering skin that resembles a burn/scald

Question 17

What are superantigens?

Answer 17

Microbial products that have the ability to promote massive activation of immune cells (can activate 1/5 T cells), resulting in a CYTOKINE STORM and inappropriate immune responses

Question 18

Diagnostic criteria of toxic shock syndrome?

Answer 18

Fever (39˚C)

Diffuse Macular Rash and desquamation (diffuse macular erythroderma)

Hypotension (≤90mmHg in adults)

≥3 organ systems involved, e.g: liver, blood, renal, mucous membranes, GI, muscular, CNS

Question 19

Diseases caused by PVL?

Answer 19

Assoc. with severe skin infections, e.g: recurrent furunculosis, sepsis/necrotising fasciitis

Question 20

What is CA-MRSA and what diseases is it responsible for?

Answer 20

MRSA bacteria causing infection in people who have not been hospitalized/had a medical procedure within the last year is called CA-MRSA

PVL and α-toxin linked with CA-MRSA responsible for necrotising pneumonia and contagious severe skin infections

Question 21

Progression pathway of necrotising pneumonia?

Answer 21

Proceeds from mild to severe:
Preceding influenza-like syndrome
Necrotising haemorrhagic pneumonia

RAPID PROGRESSION to:
Acute Resp Distress 
Deterioration in pulmonary function
Refractory hypoxaemia
Multi-organ failure despite antibiotic therapy

Question 22

What is GAS?

Answer 22

Group A β-haemolytic Strep.. is Strep. pyogenes

Question 23

3 examples of skin infections caused by Strep. pyogenes? Give a description

Answer 23

Impetigo usually affects the face; it is highly contagious through contact with discharge on the face

Cellulitis (general term) is a deeper skin infection, in the dermis, but are not assoc. with necrosis

Erysipelas is more localised that and superficial than cellulitis and is accompanied by fever, rigors and nausea

Necrotising fasciitis (flesh-eating bug) caused by invasive Strep A strains that penetrate mucous membrane and develop in the lesion; they rapidly destroy connective tissue

Toxic shock like syndrome (TSLS) is caused by pyrogenic exotoxins (SpeB and SpeC) and is a consequence of invasive infections; progresses from hypotension to organ failure

Question 24

Virulence factors produced by Strep. pyogenes?

Answer 24

Superantigenic toxins

Haemolysins (SLO, SLS) cause tissue damage and ulcers

Bacterium is surrounded by a CAPSULE (composed of hyaluronic acid), protecting it from phagocytosis by neutrophils, also, the capsule and several factors embedded in the cell wall, inc. M PROTEIN, facilitate attachment to host cells by binding:
Factor M
Fibronectin
Fibrinogen
Albumin

Question 25

How is Group A further subdivided as part of the Lancefield system?

Answer 25

System groups catalase-negative, coagulase-negative bacteria based on serotyping of their cell wall carbs

Group A is subdivided according to M protein antigens:
M1 and M3 are major serotypes

Question 26

What is streptolysin S (SLS)?

Answer 26

Pore-forming cytolysin that is toxic to PMN (polymorphnuclear cells), organelles and platelets; it is involved with tissue/cell destruction

Question 27

Two different bacteria causing TSLS and differences?

Answer 27

Staph. aureus causes a localised infeciton with no bacteraemia

Strep. pyogenes causes an invasive disease, e.g: from initial pharyngitis

Both are caused by pyrogenic exotoxins

Question 28

What are bacteriophages (informally, phage)?

Answer 28

Virus that infect and replicate within a bacterium; they are composed of proteins that encapsulate a DNA or RNA genome, e.g:
TSST-1 (S. aureus)
SEA (S. aureus)
SpeA and SpeC (S. pyogenes)