Pathogenecity of Staph Aureus Flashcards
What are the nonspecific characteristics of s. aureus making it a successful apthogen
Ability to colonise skin esp. miost - opportunistic infectinos
Resistanct to dessication
Very adaptable - cal develop anitbiotic resistance
Cyclinc of predominant types - would be useful in evading the immune response
Describe the s. auerus genome structure
2/3 core genome –> this is clonal with point mutatiosn accounting for the majority of variation and recombination rare
1/3 acessory genome - high peropeortion of mobile elemtnsl genomic/pathogenicity islands, bacteriophages, plasmids and transposons. Reassortment occurs due to hosizontal exchange
What virulence factors are encoded in the core genome
Coagulase
Protein A
Alpha haemolysin
Fibrinogen binding protein
What virulence factors are encoded in the accessory genome
Enterotoxins Toxic shock toxins Antibiotic resistance genes Leucocidins Exfoliative toxins Collagen adhesin proteins
What are the cell envelope virulence factors
1) capsule
2) protein A
3) Clumping factors ( a cell bound coagulae +/- fibringoen binding protein)
4) other cell wall associated adhesions
What is the s. aureus capsule
A thin lauer of uronic acid containing polysaccharides
Present in most clnical isoltes
Impedes phagocytosis by masking cell wall components e.g. teichoic acid
How many seroligcally distinguished types of S. Aureus are there
13
5 or 8 account for >70% of blood isolates though
What is protein A
It is a cell wall associated protein projecting from S. Aureus
Protein A binds the Fc domain of IgG and incapacitates it!
Also secretes Sbi protein binds the Fc domain of IgG
What are MSCRAMMS
Microbial Surface Components Recognising Adhesive Matrix Molecules
Name some MSCRAMMS
1) Protein A
2) clumping Factors (fibrinogen binding portein
3) Fibronectin binding protein
4) Collagen binding protein
What do the MSCRAMMS do
They each have a domain for binding target proteins
upon binding a conformational shape change occurs to increase their affinity for the moecule and sometimes to other molecuels
What does the sortase enzyme do
The sortase enzyme catalyses transpeptidisation ractions between the PXTG motif of adhsind and pentaglysine cross bridges of peptidoglycan to anchor the surface proteins to the cell wall
deficient in sortase = less virulent
Describe the enzymes as virulence factors
Coagulase - initiates fibrin polymerization by binding prothrombin
Staphylokinase
Hyalourindase - breaks down tissues of dermis in particularly
Lipase
Describe toxins as virulence factors
Haemolysins Leucocidins enterotxins Exfoliative toxins Staohpylococcal toxic shock syndrome
What do alpha and gamma haemolysisn and leucocidins form
Form multimeric beta barrel pores in host cell membranes composed of 7 identical subunis
What are the gamma toxins and leucocidins including PVL comprosed of
Comprised of the F & S polypeptides that assemble in the cell membrane to form a 7-mer structure –> resemble a beta barrel pore
What is PLV associated with
Severe necrotising skin infections and penumonias
What are PSMs
They are amphipathic and alpha helical peptides
What are the groups of PSMs
4 x PSMs alpha - 21-22a.a coded in a gene cluster
2 x psm beta - 44 aa peptides in a second cluster
PSM Delta - a delta haemolysin - 26 a.a. encoded in a 2nd gene cluster
PSM - mc - a 20 a.a encoded on some SCC Mec elements but less common
How d PSMs cause virulence
Stimualtes neutrophils to increase chemotaxis, increase cell lysis and increase IL-8
What is the sign you get in SSSS
Nikolskys sign - extensive blistering and desquamation on gentle rubbing
What are the 2 disaese mediated by exfoliative toxins
1) Bullous impetigo
2) SSSS
What are the 2 s. aureus exfoliative toxins
1) ETA - heat satble, gene on chromosmal temperate phage
2) ETB - heat labile and on plasmid
Only 40% sequence homology but serologically distincyt but functionally similar
How do the exfoliative toxins work
They bind to keratohylin structures in the stratum granulosum
The toxins have an active site with sequence homology to a trypsin like serine protease –> cleaves desmoglein - 1 which is a cell-cell adhesion molecule!
