Pathogenesis of
S. aureus infections
Staphylococcus aureus causes a variety of suppurative (pus-forming)
infections and toxinoses in humans. It causes superficial skin lesions
such as boils, styes and furunculosis; more
serious infections such as pneumonia, mastitis, phlebitis,
meningitis, and urinary tract infections; and deep-seated
infections, such as osteomyelitis and endocarditis.
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
by releasing enterotoxins into food, and toxic shock syndrome
by release of superantigens into the blood stream.
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, clotting factor);
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.
FIGURE 2. Virulence
determinants of Staphylococcus aureus
For the majority of diseases
caused by 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 a particular diseases. 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. With some staphylococcal toxins, symptoms
of a human disease can be reproduced in animals with the purified
protein toxins, lending an understanding of their mechanism of action.
Human staphylococcal
infections are frequent, but usually remain localized at the portal of
entry by the normal host defenses. The portal may be a hair follicle,
but usually it is a break in the skin which may be a minute
needle-stick or a surgical wound. Foreign bodies, including sutures,
are readily colonized by staphylococci, which may makes infections
difficult to control. Another portal of entry is the respiratory
tract. Staphylococcal pneumonia is a frequent complication of
influenza. The localized host response to staphylococcal infection is
inflammation, characterized by an elevated temperature at the site,
swelling, the accumulation of pus, and necrosis of tissue. Around the
inflamed area, a fibrin clot may form, walling off the bacteria and
leukocytes as a characteristic pus-filled boil or abscess. More
serious infections of the skin may occur, such as furuncles or
impetigo. Localized infection of the bone is called osteomyelitis.
Serious consequences of staphylococcal infections occur when the
bacteria invade the blood stream. A resulting septicemia may be
rapidly fatal; a bacteremia may result in seeding other internal
abscesses, other skin lesions, or infections in the lung, kidney,
heart, skeletal muscle or meninges.
FIGURE 3. Sites of
infection and diseases caused by Staphylococcus aureus
Adherence to Host Cell
Proteins
S. aureus cells express on their
surface proteins that promote attachment to host proteins such as
laminin and fibronectin that form the extracellular matrix of
epithelial and endothelial surfaces. In addition, most strains express
a fibrin/fibrinogen binding protein (clumping factor) which promotes
attachment to blood clots and traumatized tissue. Most strains of S.
aureus express both fibronectin and fibrinogen-binding proteins. In
addition, an adhesin that promotes attachment to collagen has been
found in strains that cause osteomyelitis and septic arthritis.
Interaction with collagen may also be important in promoting bacterial
attachment to damaged tissue where the underlying layers have been
exposed.
Evidence that staphylococcal
matrix-binding proteins are virulence factors has come from studying
defective mutants in adherence assays. Mutants defective in binding to
fibronectin and to fibrinogen have reduced virulence in a rat model
for endocarditis, and mutants lacking the collagen-binding protein
have reduced virulence in a mouse model for septic arthritis,
suggesting that bacterial colonization is ineffective. Furthermore,
the isolated ligand-binding domain of the fibrinogen, fibronectin and
collagen receptors strongly blocks attachment of bacterial cells to
the corresponding host proteins.
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