GRAM POSITIVE COCCI - STAPHYLOCCOCI AUREUS CLASSIFICATION · Kingdom = bacteria, family = staphylococcae · 0.5 - 1 um diameter · Facultative anaerobes - grow in anaerobic or aerobic conditions · 18 - 40°C · Catalase positive - can break down H2O2 · Major differentiating feature = coagulase · Ability to coagulase citrated plasma · Yes = staph aureus · No = staph epidermis / sacrophytious STAPHYLOCOCCUS AUREUS MECHANISM OF INFECTION 1. Colonisation of the host · MSCRAMMS (microbial surface components recognising adhesive matrix molecules) = mediate the initial attachment of bacteria to host tissue by producing: · Fibronectin and laminin = allows binding to healthy skin · Fibrin and fibrinogen = promotes adhesion to damaged tissue and blood clots · Collagen binding protein = promotes adhesion to severely damaged tissue 2. Avoidance of host defences · Caspular polysaccharide = prevents phagocytosis so is therefore a virulence factor . Protein A = locks antibody the wrong way round - antibody sponge · Leukocidin = panton valentine leukocidin (PVL) = pore forming toxin, WBC destruction 3. Invasion of host tissue via invasins: · Membrane damaging toxins · Coagulase = clotting around pathogen - protects from phagocytosis · Staphylokinase (SAK) = activates plasminogen to form plasmin which digests fibrin clots - bacterial spread · Hyaluronidase = lyses hyaluronic acid, destroys polysaccharide - bacterial spread · DNase = splits DNA - nutrition · Fatty acid modifying enzyme (FAME) = converts bacterial FA in infected tissue to alcohols (e.g. cholesterol) - alleviates bactericidal effect 4. Production of exotoxins · Enterotoxins (A-E, G-T) = 65% of strains, toxins ingested, profuse vomiting · Toxic shock syndrome toxin (TSST-1) = 5-25% of strains, toxins produced systemically · Exfoliative toxic (ETA/ETB) = 5-10% of strains, toxins produced systemically (serine proteases), scalded skin syndrome . They're all 'superantigens' meaning they bind non-specifically to MHC class Il on antigen presenting cells · 1/5 T cells activated, increased cytokine release, interleukins, toxic shock - highly inflammatory response MRSA . S. aureus and MRSA have different binding sites - PBP and PBP2a respectively . PBP2a has a lower affinity · MecA (30-50kb) incorporated on SCCmec (staphylococcal cassette chromosome mec) which is mobile genetic info, transmissible by conjugation · Vancomycin = drug of choice for treatment
VANCOMYCIN · Interferes with cell wall synthesis by binding to D-ala-D-ala in peptidoglycan, preventing addition of new wall subunits · Blocks transglycosidase and transpeptidase enzymes · Vancomycin intermediate s.aureus (VISA) · First reported in Japan (1996) . Possess mecA gene and have a thicker cell wall therefore acting as a sponge, trapping vancomycin in the established peptidoglycan · Fully resistant VRSA found in USA 2002 · Possess mecA and vanA gene (D-ala-D-lac instead) · VanA gene = plasmid based therefore potential for HGT (horizontal gene transfer) between MRSA CLINICAL MANIFESTATIONS · 40% carriage rate of s.aureus · 1-2% carriage rate of MRSA · Superficial infection = pus, boils, CVC, inflammation, · Deep infection = diabetic leg ulcer · Systemic = scalded skin syndrome · Neonates and small