Staph aureus Flashcards
<p>Describe bacteriology of staphylococci </p>
<p>- small, gram positive bacteria
- cocci that grow in grape like clusters
- facultative anerobes
- catalase positive and oxidase negative</p>
<p>What are the three Staph that cause disease in humans</p>
Describe catalase test - what would be the result?
all staph produce catalase so the test would be positive.
the test is performed by adding hydrogen peroxide to a colony on an agar plate - if catalase positive they will produce oxygen bubbles at once
Describe coagulase
coagulase is an extracellular protein secreted by S. aureus that is it’s traditional marker in the clinical lab.
it causes local blood clotting by convertin prothrombin to thrombin which will then convert fibrinogen to fibrin.
it acts as a virulence factor by coating the bacteria with fibrin to disguise them from immune cells.
What re the two main surface proteins of S. aureus
clumping factor - promotes attachment to blood clots by binding to fibrinogen. it allows bacterial invasion of wounded surfaces.
protein A - binds Fc region of antibodies and inhibits their function
List the three diseases caused by S. aureus and their respective exotoxins
- Gastroenteritis - caused by food contaminated with enterotoxins A-I
- Toxic shock syndrome - caused by TSST-1
- Scalded skin syndrome - caused by exfoliation toxins A, b and d.
Describe Gastroenteritis
- inflammation of stomach and intestinal mucosa.
- caused by food contaminated with enterotoxins A-I
- symptoms include nausea vomiting and diarrhoea with rapid onset after ingestion
- enterotoxins are heat stable so cooking food will not kill them, they are also resistant to drying.
- spontaneous recovery after 24h
Describe toxic shock syndrome
- caused by superantigen TSST-1.
- superantigens will activate a large number of Th cells by cross linking them to APCs without normal Ag recognition.
- this leads to cytokine storm which can be dangerous.
- seen in menstruation where S. aureus replicates in blood soaked tampons and release its toxin.
- life threatening disease - symptoms include sudden shock, high fever, nausea, vomiting and renal/hepatic dysfunction
- without treatment - bp will rapidly drop, leading to coma and eventually death
Describe Scalded skin syndrome
- caused by exfoliation toxins A, b and d.
- they are serine proteases which will cause the epidermis to split just below the dead keratinised outer layer.
the protease cleaves the desmosome junctions between ECs - this results in exfoliation/peeling of skin.
it causes the skin to appear burnt and tender to touch. - occurs mainly in infants.
- other symptoms include malaise, irritability and fever.
What are diseases caused by direct organ invasion?
Pneumoniae - rare but can occur in some severe cases of community acquired S.pneumoniae, often follows viral infection.
Meningitis
Osteomyelitis - bone infection, mainly seen in children <12
Endocarditis - infection of heart valves leading to their rapid destruction
Septic arthirits - infection of join cavity - most common pathogen causing disease in elderly.
skin infections
Describe peptidoglycan
o It’s the material found only in bacteria and is reason behind strength of cell wall.
o It’s vital for the cell’s growth and survival.
o alternating series of N-acetylmuramic acid and N-acetylglucosamine which are covalently joined.
Each of NAM/NAG are attached to a tetrapeptide chain which also connect together.
There are a group of enzymes that act to catalyse formation of peptide bridges - an important step of peptidoglycan synthesis. Called penicillin binding proteins (PBP)
Describe penicillin’s mechanism of action and resistance towards it
Member of the β-lactam drugs which inhibit peptide bridges.
Binds to the four different PBPs of S. aureus – which are mostly transpeptidases.
It covalently binds to these PBPs, this degrades peptidoglycan and causes the cell to lyse.
Resistance: β-lactamase (penicillinase) is secreted by S. aureus which cleaves the β-lactam ring of penicillin, rendering it inactive so it can no longer bind to PBPs.
Gram negative bacteria produce different β-lactamase than gram positive.
Describe methicillin and resistance towards it (MRSA)
Also a member of the β-lactam drugs, however it cannot be inactivated by penicillinase - was developed after S. aureus was found to be resistant to penicillin.
However 40% of S. aureus have acquired the ability to produce an altered PBP2A which has a low affinity for binding methicillin – it’s of the HMW class.
These bacteria are referred to as MRSA - Methicillin resistant Staphylococcus aureus.
They are treated with vancomycin, an antibiotic of last resort.
Recently some strains have emerged that are resistant to normal levels of vancomycin. Hospital guidelines have so far managed to control the emergence of these strains.
How can whole genome sequencing be used to detect MRSA outbreaks
The emergence of MRSA can cause hospital outbreaks which makes it necessary to understand transmission patterns.
Example - in a baby care unit in Cambridge, they sequenced isolates from all colonised patients and sequenced MRSA isolates from patients in the hospital or community with the same antibiotic susceptibility profile as the outbreak strain.
The outbreak was a new sequence type and was confirmed to have been spread by staff member in the hospital.
WGS can be used to investigate small-scale evolution of MRSA bacteria.
