Staphylococcus aureus forms a fairly large yellow colony on rich medium; S. aureus is often hemolytic on blood agar; Staphylococci are non-motile, non-spore forming facultative anaerobes that grow by aerobic respiration or by fermentation that yields principally lactic acid. The bacteria are coagulase-positive and catalase-positive. S. aureus is a mesophile, with a heightened resistance to heat. S. aureus can grow at NaCl concentrations as high as 15 percent, as well as at high concentrations of acid.  S. aureus is resistant many antibiotics and disinfectants.

Staphylococcus aureus causes a variety of suppurative (pus-forming) infections and toxinoses in humans. It causes superficial skin lesions such as boils, styes and furuncles; more serious infections such as pneumonia, meningitis, and urinary tract infections.  S. aureus is a major cause of hospital acquired (nosocomial) infection of surgical wounds and infections associated with indwelling medical devices. S. aureus causes food poisoning and toxic shock syndrome. The toxins mostly responsible for causing these infections and diseases in humans are the superantigens and alpha-toxins.  The alpha-toxins oligomerize to form pores in the host cellular membrane, allowing cellular contents to leak into the extracellular matrix.  The superantigens, consisting of enterotoxins and the toxic shock syndrome toxin, are responsible for S. aureus-related food poisoning and toxic shock syndrome, respectively. (See Figures 1 for how alpha-toxins and superantigens work)
 
 
 
 

 Protein Structure:
 
 Structure of alpha-toxins, one of the major components of S. aureus's toxicity and pathogenesis to humans.

Toxic Shock Syndrome Toxin 1 (TSST-1):

At the Molecular Level

S. aureus expresses many potential virulence factors: (1) surface proteins that promote colonization of host tissues; (2) invasins that promote bacterial spread in tissues (leukocidin, kinases, hyaluronidase); (3) surface factors that inhibit phagocytic engulfment (capsule, Protein A); (4) biochemical properties that enhance their survival in phagocytes (carotenoids, catalase production); (5) immunological disguises (Protein A, coagulase); and (6) membrane-damaging toxins that lyse eukaryotic cell membranes (hemolysins, leukotoxin, leukocidin; (7) exotoxins that damage host tissues or otherwise provoke symptoms of disease (SEA-G, TSST, ET); (8) inherent and acquired resistance to antimicrobial agents.

Virulence Factors and the Effects on Cells:

Fibronectin, a surface protein, promotes adherence of the bacteria to the host cell.  Once adhered to the cell, the bacterium can become internalized in a phagocytosis-like processes.
Capsule, a surface polysaccharide, inhibits the host phagocytotic immune response, thereby prolonging the life of the bacterium within the cell.
Protein A binds to immunoglobin G molecules, thereby disruping host phagocytosis.
Leukocidin also prevents phagocytosis.
Hemolysins and leukotoxins release toxins that damage host cell membranes, causing cell lysis.
Exotoxins are responsible for most symptoms observed during infection.
Enterotoxins (six antigenic types) and toxic shock syndrome toxin (TSST-1) cause toxic shock.
Alpha-toxin causes septic shock.
 
How the virulence factors above play a role in the conditions that most commonly result from a S. aureus infection:

Food poisoning (emesis or vomiting)
Toxigenesis: Enterotoxins A-G
Septicemia (invasion of the bloodstream)
Invasion: staphylokinase, hyaluronidase, other extracellular enzymes (proteases, lipases, nucleases, collagenase, elastase, etc.)
Resistance to phagocytosis: capsules, coagulase, protein A, leukocidin, hemolysins, carotenoids, superoxide dismutase, catalase, growth at low pH
Resistance to immune responses: coagulase, protein A, antigenic variation
Toxigenesis: cytotoxic toxins (hemolysins and leukocidin)

Toxic shock syndrome
Colonization: cell-bound (protein) adhesins
Resistance to immune responses: coagulase, antigenic variation
Toxigenesis: TSST toxin, Enterotoxins A-G (pyrogenic exotoxins)

Surgical wound infections
Colonization: cell-bound (protein) adhesins
Invasion: staphylokinase, hyaluronidase, other extracellular enzymes (proteases, lipases, nucleases, collagenase, elastase, etc.)
Resistance to phagocytosis: coagulase, protein A, leukocidin, hemolysins, carotenoids, superoxide dismutase, catalase, growth at low pH
Resistance to immune responses: coagulase, protein A, antigenic variation
Toxigenesis: cytotoxic toxins (hemolysins and leukocidin)
 
S. Aureus Genome
For the majority of diseases caused by this S. aureus, pathogenesis is multifactorial, so it is difficult to determine precisely the role of any given factor. However, there are correlations between strains isolated from particular diseases and expression of particular virulence determinants, which suggests their role in particular diseases. With some exotoxins, symptoms of a human disease can be reproduced in animals with the pure proteins. The application of molecular biology has led to advances in unraveling the pathogenesis of staphylococcal diseases. Genes encoding potential virulence factors have been cloned and sequenced, and many protein toxins have been purified.

Phagocytosis is the major mechanism for combatting staphylococcal infection. Antibodies are produced which neutralize toxins and promote opsonization. However, the bacterial capsule and protein A may interfere with phagocytosis. Biofilm growth on implants is also impervious to phagocytosis

Treatment

Treatment of non-hospital acquired S. aureus infections, showing no signs of broad-antibiotic resistance, is achieved with a cocktail of penicillin and penicillin-derived antibiotics, including some of the following: flucloxacillin, gentamycin, rifamicin, fusidic acid, erythromycin, vancomyin, and cefotaxime. However, ninety percent of Staphylococcus strains are resistant to penicillin and penicillin-derived antibiotics, with hospital-acquired S. aureus being entirely resistant to penicillin and penicillin-derived antibiotics. These require more aggressive antibiotic treatments with methicillin and vancomycin being the only available treatment options.

Diagram adapted from www.bact.wisc.edu/Bact330/lecturestaph
 
Vaccines:
No vaccine is yet available that stimulates active immunity against staphylococcal infections in humans. A vaccine based on fibronectin binding protein induces protective immunity against mastitis in cattle and might also be used as a vaccine in humans.

Hyperimmune serum or monoclonal antibodies directed towards surface components (e.g., capsular polysaccharide or surface protein adhesions) could theoretically prevent bacterial adherence and promote phagocytosis by opsonization of bacterial cells. Also, human hyperimmune serum could be given to hospital patients before surgery as a form of passive immunization.

When the precise molecular basis of the interactions between staphylococcal adhesins and host tissue receptors is known it might be possible to design compounds that block the interactions and thus prevent bacterial colonization. These could be administered systemically or topically.

In February, 2002, an experimental bivalent vaccine against Staphylococcus aureus was reported to be safe and immunogenic for approximately 40 weeks in patients with end-stage renal disease undergoing hemodialysis. The vaccine called StaphVAX is composed of S. aureus type 5 and 8 capsular polysaccharides conjugated to nontoxic recombinant Pseudomonas aeruginosa exotoxin A. In randomized trials, one injection of the vaccine was administered to 892 hemodialysis patients. Between weeks 3 and 40, 11 cases of S. aureus bacteremia were diagnosed in the vaccinated group compared with 26 cases in a control group. Nearly 90% of patients receiving the vaccine generated antibodies to the two capsular polysaccharides.  A decrease in vaccine efficacy after week 40 correlated with a decrease in S. aureus antibodies. The investigators did not believe that use of StaphVAX would be limited to hemodialysis patients. For example, the vaccine might be used in cases where healthy individuals come into the hospital for elective surgery, such as a joint replacement. Such patients do not require protection for the rest of their lives; what they need is protection for a short period while they are in the hospital. The vaccine manufacturer will experiment with booster shots to maintain immunity for longer periods of time, and with passive immunization for such at-risk populations as premature infants. They hope to gain FDA approval for the vaccine in 2006.
 
Figure1
Diagrams from http://gsbs.utmb.edu/microbook/ch012.html

How Superantigens work
 
S. aureus produces two types of superantigens, enterotoxins and toxic shock syndrome toxin.  Superantigens stimulate T-cells nonspecifically, causing the release of large amounts of cytokines.

How alpha-toxins work:
 
 

References:

http://www.bact.wisc.edu/Bact330/lecturestaph

http://www.molbio.princeton.edu/courses/mb427/2001/projects/02/staph.htm

http://www.cryst.bbk.ac.uk/sagdb/sagdb.html