Lecture 1 - Staphylococcus Flashcards
Which surgeon noticed some post surgical infections. In absecesses recover adn visualise organisms to look like bunches of grapes
William Ogston 1881
First description of staph
3 years after Ogston what did anton rosenbach do
Classify organisms from absseces into two groups - golden colonies on agar and smaller white colonies
Can s.epidermidis cause disease
No it is non pathogenic
What is the size of the staphylococci
0.5-1 um
Is staphylococcus catalase + or negative
Catalase positive
Are staphylococcus aerobic or anaerobic
FACULTATIVE ANAEROBE
What can differentiate s aureus from other staph
Coagulase positive
What does s aureus do with coagulase
Coagulate CITRATED PLASMA
CONVERT FIBRINOGEN TO FIBRIN - SURROUND ORGANISM WITH HUGE FIBRIN CLOT FOR PROTECTION FROM ANTIBIOTICS ETC
Name the three main virulence factors that staph areus has (basic)
1- adhesins - cell bound proteins (ATTACHMENT)
2- Protein A and microcapsule (EVASION)
3- Toxins and Invasins (DAMAGE HOST)
Name the three toxins produced and what effect they have
- TSST
- EFT
-SE A-G
Enterotoxins so cause vomiting.
Cause toxic shock( multifunction organ failure), exfoliation (skin blistering) and emesis (vomiting)
What antibody binds to protein A
IgG
Describe in detail how staph aureus colonise host
MSCRAMMS - microbial surface components recognising adhesive matrix molecules
A) expression of surface fibronectin and laminin binding proteins -
Fibronectin, laminin (and fibrinogen) form extracellular surface matrix of HEALTHY endothelial and epithelial surfaces (hence carriers of s.aureus if can bind to healthy tissue)
B) Expression of fibrin/fibrinogen binding proteins (clumping factor) - promotes adhesion to DAMAGED tissue and BLOOD CLOTS.
C) Expression of collagen binding protein - promotes adhesion to SEVERELY DAMAGED tissue. Collagen deeper in tissue.
In detail how does staph aureus evade host defences
CASPSULAR POLYSACCHARIDE - aka microcapsule.
Protein A - prevent c3b of complement attaching to surface of bacteria so prevent complement associated oxidation phagocytosis. It binds IgG WRONG WAY ROUND via Fc receptor instead of FAB
Leucocidin - pore forming toxin. protein toxin burst open wbc . Genes carried by bacteriophage injected into staph chromosome. PVL (Panton Valentine - Leucocidin) can burst open cell
What % carry lethal form of leucocidin
1-2%
How does staph aureus invade tissue
- membrane damaging toxins (alpha - haemolysin - type II toxin attack membrane )
- coagulase - clotting protective layer
- staphylokinase - fibrinolysis; bacterial spread (break down clot so can spread through tissue)
- hyaluronidase -lyses hyaluronic acid (as ECM make up of HA - can spread through ECM now)
- DNAase - split for nutrition
- Fatty Acid Modifying enzyme (FAME) - converts bacterial FA in infected tissue to alcohols e.g. Cholesterol
What are the enterotoxins produced by 60-70% of s aureus
A-E, G-J
Toxins INGESTED through contaminated food stuffs (custards, pastries, milk )
- food poisoning (profuse vomiting)
-HEAT STABILE at 100 deg for several minutes. S aureus may die but toxin live
What does the toxin TSST-1 do that some s aureus produce
Toxic shock syndrome toxin (TSST-1)
- toxins produced systemically
Associated with tampon use early 80s
Fever, shock, skin rash , multi system involvement
Carry sa in genital tract so don’t change tampons get this
What does exfoliative toxin do that some s aureus produce
Exfoliative A and B (ETA and ETB)
Toxins produce systemically (serine proteases split dermal junctions in skin and cause severe blistering. May start as little pimple lead to big blistering. )
- hence SCALDED SKIN SYNDROME
The s aureus exotoxins (enterotoxins A-E, G-J, TSST-1 and exfoliative toxins) are all superantigens. What does this mean
They all bind non specifically to MHC class II of antigen presenting cells
- AVOID DIGESTION PROCESS
- As it is non specific massive amount of t cells so increased cytokine release TNF, interleukins, get INF = toxic shock.
TYPE I TOXINS
What is the difference in ratios of t cell activation for normal antigen and super antigen
Normal - 1:10,000 T cells activated
Superantigen - 1:5 T cells activated
Briefly describe mrsa history
Methicillin a beta Lactam antibiotic introduced in 1960 to withstand beta lactamase producing staph
- MRSA: first described in 1961 ; recognised as a hospital pathogen in 70’s - rapid spread through hospitals 1980-2005
- if found in hospitals it is HA-MRSA if found in community, healthcare workers, and patients then (CA-MRSA)
- transmission patient to patient, environment to patient and HCW. To patient
What percentage of s areus are now mrsa
50%
How does s aureus become mrsa
MecA gene incorporated on SCCmec gene (staphylococcal cassette chromosome mec)
Encodes for additional pencilling binding proteins (PBP2a) ; reduced affinity for beta lactams
MRSA resistant to all beta lactam antibiotics
What is drug of choice for mrsa
Vancomycin - drug of choice - glycopeptide bind to D-ala D-ala. work at membrane level. Blocks action of transglycosidase and PBP enzymes (transpeptidase)
Prevent new wall subunits being added
What is visa
MRSA with reduced suscpetilbity to vancomycin
Vancomycin intermediate Staph aureus (VISA)
First strains reported in Japan 1996
What does visa posses to make it slightly resistant to vanco
Possses Meca gene AND cell wallthicker than usual acting as a sponge to trap Vancomyocin in established peptidoglycan
How can we attempt to resolve visa
Give even more vancomycin but this drug has side effects
What is the type of mrsa to be fully resistant to vancomycin
VRSA - USA 2002
WHAT DOES VRSA HAVE
Posses mecA gene aAND VANA gene encode for altered resistant cell wall structure from D-ala D-ala to D-ala D-lac
Van A genes are plasmid based; proteintial for HGT between MRSA (conjugation.)
Believed to have received VanA from vancomycin resistant enterococcus which is in our gut
What is carriage rate of s aureus and MRSA
40% carriage rate of s aureus in healthy individuals
1-2% carriage rate MRSA
What are 3 types of MRSA infection
Mild superficial (skin)
Deep (organs, tissue, bone)
Systemic (including toxaemia)
Purulent infections
Name some sites of infections and the disease you get there
Heart - endocarditis Bones - osteomyelitis Vagina/cervix - cystitis, TSS Skin - impetigo Eye - Stye Lungs - pneumonia Gut - emisis
What are predisposing factors for s aureus infection
Carriage of organism Diabetic patients Immunsupporessed patiets Drug users Hospital stay Intrvascular catheters
What are the clinical manifestations of s aureus infection (syperificial)
Staphylococcal boils
Surgical wound infection show inflammation and pus
What is seen in an superficial infection associated with central venous catheters (CVC)
Localised CVC infection. Inflammation, exudate, erythema
Where can deep seated staphylocall infections occur (two examples)
Skin and tissue destruction of diabetic leg ulcer
Discharging staphylococcal sinus in cancer patient
Describe a systemic skin infection (Scalded skin syndrome SSS) - toxin associated
- follows localised focus of infection e.g, skin
- s aureus infection and toxin production (superantigen)
Splitting of skin, erythema and blisters
-affects neonates and young children (reduced immunity) - mortality rate approx 4%
