1 Bacterial pathogenesis Flashcards
Pathogenicity
capacity of a microbe to cause damage in a host
Virulence
relative capacity of a microbe to cause damage in a host (severity)
Virulence factor
molecule produced by microbe that promotes pathogenicity
Bacteria disease host responses
- Colonisation – adhesion, nutrient acquisition (produces lots of enzymes to acquire these)
- Invasion of tissues
- Avoidance of host defences
- Tissue damage
- Transmission
S. aureus gram stain
Gram purple – retain crystal violet due to thicker peptidoglycan layer
positive facultative anaerobe
S. aureus size and shape
Cocci, 1µm diameter
S. aureus resistance
Some strains are resistant to all known antibiotics
how many are carriers of S. aureus
part of normal microflora
20% persistent
60% intermittent
what type of pathogen is S. aureus
commensal
or
Opportunistic pathogen that can cause a wide range of diseases
Examples of staphylococcus diseases
Pimple
Impetigo
TSS
S. aureus transfer
Horizontal gene transfer can occur – e.g plasmids, transposons, pathogenicity islands, bacteriophage, SCCmec
S. aureus and environment
Organism is continually changing and adapting in response to its environment
Antibiotic Resistance - S. aureus
Staphylococcal antibiotic resistance is a major problem particularly in hospitals.
Methicillin Resistant S. aureus (MRSA)
what causes S. aureus resistance
production of a new penicillin binding protein (PBP2a) encoded on SCCmec
what is SCCmec
Staphylococcal cassette chromosome mec
what does SCCmec do
Mobile genetic (moved around by bacteriophage) element that integrates at the attB phage site of S. aureus chromosome
what is HA-MRSA
Hospital Acquired MRSA
why is S. aureus resistant to b-lactams antibiotics
“accumulation” of lactamase
what is the drug of choice for MRSA infection
Vancomycin
what is VISA or GISA
S. aureus with reduced sensitivity to vancomysin have been isolated
Called VISA or GISA strains = vancomycin/glycopeptide intermediate S. aureus
what is VRSA
vancomycin resistance has been found in a small number of S. aureus
CA-MRSA strains
strains are genetically more diverse (exposed to varying bacteria) than hospital acquired MRSA
what is CA-MRSA associated with
SCCmec type IV and V elements
what are CA-MRSA usually resistant to
Type IV and V SCCmec elements only usually confer resistance to b-lactams
CA-MRSA resistance
usually not multiple resistant, but now evidence that some SCCmec Type V strains are resistant to non - b-lactams
those at risk to CA-MRSA
Young – children and young adults
Contact sports - skin abrasion (MMA/ Wrestling)
Sharing towels and athletic equipment
weakened immune systems e.g HIV/AIDS patients
example of attachment to host cells
fibronectin binding proteins
evasion of host immune system examples
Protein A
Chemotaxis inhibitory protein
invasion and spread - exotoxins
alpha toxin
panton-valentine leukicidin
Conditioning films
biomaterials are implanted into tissue, the very quickly become coated with host ECM proteins e.g fibrinogen, fibronectin
Examples of S. aureus adhesin
FnbA/B - Fibronectin binding proteins
Cna - Collagen binding protein
what is MSCRAMMS
Microbial Surface Components Recognising Adhesive Matrix Molecules
other S. aureus adhesins
IsdA
Eap
Emp
IsdA adhesin
iron regulated surface determinant A
what does IsdA do
- Broad spectrum adhesin
- Binds to fibronectin and fibrinogen
- Expression is iron regulated
Eap adhesin
Extracellular Adherance protein
what does Eap do
- Broad spectrum adhesin
- Binds to fibronectin, fibrinogen and vitronectin and promotes internalisation of S. aureus into epithelial cells
- Expression is iron regulated
Emp adhesin
Extracellular matrix protein binding protein
what does Emp do
- Broad spectrum adhesin
- Expression is iron regulated
alpha hemolysin (hla)
is a cytotoxic exotoxin – help to lyse red blood cells to get iron, to use for self
how many hemolysins does S. aureus have
3
what does alpha hemolysin/toxin do
Membrane depolarisation – form holes in RBC
what does PVL cause
These strains caused serious skin and soft tissue infections and pneumonia – pneumonia rapidly fatal
how is PVL transferred
Bacteriophage involved in transfer - Phage transferred
PVL effect on humans
PVL is toxic for human polymorphs – causes WBC lysis, forming holes in membrane
Why do bacteria regulate virulence factors
- High metabolic burden
- Only expressed when they provide a growth or survival advantage
- Allows S. aureus to adapt to different niches within the host
How are virulence factors regulated?
Regulate at different levels
- control transcription rate
- control mRNA stability
- control translation rate
- control of protein stability
how can virulence be altered
Bacteria can alter virulence gene expression in response to a signal
Signal may be environmental are internal
External signal examples
Usually through receptor proteins on cell membrane
Nutrient limitation
pH
heat
what does quorum sensing control
virulence factor production by S. aureus
Why will bacteria make different decisions
depending on what regulators they have
why can S.aureus cause a variety of infections
vast number of virulence factors
what affects virulence gene expression
Environmental factors affect virulence gene expression and allow adaptation to niches within the host
what must be tightly regulated in virulence factors
temporal expression
