Molecular Basis of Bacterial Virulence Flashcards
What are virulence factors?
Molecules produced by pathogens that contribute to the pathogenicity of the organism, e.g: toxins
Describe the pathway of pathogens
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
Definition of virulence?
Capacity of a microbe to cause damage to the host; result of variation in genes
5 examples of virulence factors?
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
3 types of Staph. aureus virulence factors?
Fibrinogen Binding Protein (an adhesin)
Leukocidin (PVL - specific toxicity and killing for leukocytes)
TSST-1 is a toxin (shock, rash, desquamation)
Locations of S. aureus?
Anterior nares and perineum
In the environment, it can be acquired from the community of nosocomial (hospital)
Describe nosocomial infection with Staph. epidermidis
Associated with foreign devices, e.g:c catheters
Pathogenicity of Staph. aureus with relation to its variable presentations?
Superficial lesions can range from boils to abscesses
Systemic presentations can be life-threatening
Toxinoses (toxic shock and scalded skin syndrome)
6 presentations of Staph. aureus as a skin infection?
Rash Folliculitis Abscess Carbuncle (multilocaular abscess) Impetigo Scalded Skin Syndrome
Function of adhesins?
Extracellular matrix molecules that are present on epithelial and endothelial surfaces as well as a component of blood clots
Examples of adhesins and genes?
Fibrinogen-Binding (ClfA ClfB)
Collagen binding (CNA)
Examples of how pathogens evade host defences?
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
Definition of toxinosis?
Any disease caused by the action of a toxin, for example:
TSST-1 (Toxic Shock Syndrome Toxin - 1)
Staphylococcal food poisoning
Scalded Skin Syndrome
Symptoms of TSST-1?
Rapid progression (48 hrs) with high fever, vomiting, diarrhoea, sore throat, muscle pain
Symptoms of Staph. food poisoning?
Intoxication, vomiting and diarrhoea that are self-limiting (1-5 hrs)
Symptoms of Scalded Skin Syndrome?
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
What are superantigens?
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
Diagnostic criteria of toxic shock syndrome?
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
Diseases caused by PVL?
Assoc. with severe skin infections, e.g: recurrent furunculosis, sepsis/necrotising fasciitis
What is CA-MRSA and what diseases is it responsible for?
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
Progression pathway of necrotising pneumonia?
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
What is GAS?
Group A β-haemolytic Strep.. is Strep. pyogenes
3 examples of skin infections caused by Strep. pyogenes? Give a description
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
Virulence factors produced by Strep. pyogenes?
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
How is Group A further subdivided as part of the Lancefield system?
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
What is streptolysin S (SLS)?
Pore-forming cytolysin that is toxic to PMN (polymorphnuclear cells), organelles and platelets; it is involved with tissue/cell destruction
Two different bacteria causing TSLS and differences?
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
What are bacteriophages (informally, phage)?
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)
