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Staphylococcus aureus

Micro > Bacteriology > Gram-positive bacteria > Gram-Positive Cocci > Staphylococci
S. aureus are gram-positive cocci that lie in grape-like clusters.  It is beta-hemolytic (completely hemolyzes red blood cells on an agar plate), but can be distinguished fromother beta-hemolytic cocci by their elaboration of a golden pigment whencultured on sheep blood agar.  Like allstaphylococci, S. aureus is catalase-positive.  However, of the three pathogenicstaphylococcal species, only S. aureus is coagulase-positive.

Epidemiology:  Ubiquitous organism normally found on skinflora and mucosal surfaces and can survive for long periods on dry surfaces. Approximately 30% of humans are colonized with S. aureus in nares. Person to person spread through direct contact or exposure to contaminated clothing, objects, etc. Most infections are from a patient's endogenous flora.

Gram Stain: Gram+, catalase +, coagulase + cocci

Morphology: 0.5-1.5umin diameter spherical cells that normally appear in clusters, a golden oryellow color.

Physiology:Facultative anaerobe, non-motile, encapsulated

Key enzymes:
  • Coagulase: Fibrinogen to fibrin
  • Hyaluronidase: Hydrolizes hyaluronic acid in connective tissue allowing spread of organism
  • Fibrinolysin: Breaks down fibrin clots
  • Lipase: Hydrolize lipids
  • Nuclease: Hydrolize DNA

Virulence factors:
  • -Alpha toxin which creates cellular destruction and abscesses
  • -Exfoliative toxin which splits epidermis at stratum granulosum
  • -Toxic Shock syndrome toxin which binds to MHC II outside of      antigen binding site to cause cytokine storm - releases IL-1 and IL-2, IFN gamma and TNF alpha
  • -Enterotoxins- food poisoning and heat stable
  • -Protein A- binds Fc-IgG and inhibits opsonization and activation
  • -Panton-Valentine leukocidin creates pores in cell membranes in less than 5 percent of strains.

Culture/Testing:
Clinical presentation and staph culture confirmatory-smooth yellow colonies within 24 hours on non-selective nutrient rich agar with sheepblood. Beta hemolysis seen
Positive reactions for coagulase,protein A, heat-stable nuclease, and mannitol fermentation
Nucleic acid-based tests/ FISH also confirmatory

Pathobiology:
-General:Virulence factor expression is controlled by regulatory systems such as AGR(accessory gene regulator) which provides quorum-sensing control. Specifically,the regulator will express adherence proteins when density of bacteria is lowand toxins/hydrolytic enzymes when organism density is high.
-Adherence to host matrix proteins (elastin, collagen, etc) aremediated by adhesion proteins bound to cell wall. These MSCRAMMs (microbialsurface components recognizing adhesive matrix molecules) include staphylococcal protein A, fibrionectin-binding proteins A and B, and coagulase proteins A and B (aka clumping factors A and B which allow aggregation of organism) Slimelayer also aids in adherence
-Evasion: While staph will bind IgG and C3 opsonins in serum, the capsule protects the cell from phagocytosis by PMNs. The productionof a slime layer also hinders phagocytosis and Protein A inhibits clearance bybinding immunoglobulins.
-Toxins: Produces many which includecytolytic toxins (membrane damaging ), exfoliative toxins, enterotoxins, andtoxic shock syndrome toxin-1
  • Cytolytic toxins can also lyse neutrophils causing lysosomal enzymerelease and damage of surrounding tissue. Also act on erythrocytes,fibroblasts, leukocytes, macrophages, and platelets
  • Exfoliative toxins: Serine proteases split intercellularconnections in stratum granulosum of epidermis
  • Enterotoxins: Superantigens which stimulate T cell and cytokinerelease. Stimulates release of inflammatory mediators from mast cells-increasesintestinal peristalsis, fluid loss, nausea, vomiting
  • Toxic shock syndrome toxin- Superantigen producing leakage and cellular destruction of endothelial cells

Major associated diseases:
i. Toxin Mediated Disease
1. Staphylococcal toxic shock syndrome (STSS): because of TSST-1 toxin. May be menstrual related but not necessary. Fever, erythematous rash, desquamation, hypotension and organ failure = shock
2. Staphylococcal food poisoning: caused by enterotoxins and is quick onset and short lasting. Emesis w/ or w/o diarrhea. From poorly heated foods/foods at room temperature for too long.
3. Staphyloccal Scalded Skin Syndrome (SSSS): separation within epidermis via stratum granulosum. Exfoliative toxin A and B.  
ii. Infection Mediated Disease
1. Carbuncles, furuncles, cellulitis [although less than streptococci], abscesses, bacteremia, endocarditis, pneumonia, osteomyelitis, septic arthritis, UTI.

Treatment:
  • Oxacillin or other semisynthetic penicillins resistantto B-lactamase hydrolysis (penicillinase possessed by ~90% staph) such as methicillin, nafcillin, oxacillin, dicloxacillin
    • These will work for MSSA butnot MRSA.
  • Can also include sulfamethoxazole, doxycycline or minocycline, clindamycin or linezolid; vancomycin for IV therapy with daptomycintigecycline, or linezolid acceptable alternatives.
    • generally effective for "Methicillin Resistant Staph aureus"

Important concept: Inducible Clindamycin Resistance –check the " D Test" when the organism is known to be resistant to erythromycin.
- To check for this, a disc diffusion test must be done, placing an erythromycin disc and clindamycin disc on a lawn of growth.
- positive result looks like the letter "D" zone of inhibition
- S. aureus inducible resistance to clindamycin; clindamycin will be ineffective.
- if there is a D, then there is inducible resistance, but if there is a circle then clindamycin is probably a good treatment



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