Staphylococcus (page 4)
© Kenneth Todar, PhD
Avoidance of Host Defenses
S. aureus expresses a number of factors that have the potential
to interfere with host defense mechanisms. This includes both
structural and soluble elements of the bacterium.
The majority of clinical isolates of S aureus express a surface
polysaccharide of either serotype 5 or 8. This has been called a
microcapsule because it can be visualized only by electron microscopy unlike the
true capsules of some bacteria which are readily visualized by light
microscopy. S. aureus strains isolated from infections express high levels of the
polysaccharide but rapidly lose the ability when cultured in the
laboratory. The function of the capsule in virulence is not entirely clear.
Although it does impede phagocytosis in the absence of complement, it also
impedes colonization of damaged heart valves, perhaps by masking adhesins.
Protein A is a surface protein of S. aureus which binds IgG
molecules by their Fc region. In serum, the bacteria will bind IgG molecules in the
wrong orientation on their surface, which disrupts opsonization and
phagocytosis. Mutants of S. aureus lacking protein A are more efficiently
phagocytosed in vitro, and mutants in infection models have diminished virulence.
S. aureus can express a toxin that specifically acts on
polymorphonuclear leukocytes. Phagocytosis is an important defense against staphylococcal
infection so leukocidin should be a virulence factor.
S. aureus can express several different types of protein toxins
which are probably responsible for symptoms during infections. Those
which damage the membranes of cells were discussed previously under Invasion.
Some will lyse erythrocytes, causing hemolysis, but it is unlikely that
hemolysis is a relevant determinant of virulence in vivo. Leukocidin
causes membrane damage to leukocytes, but is not hemolytic.
Systemic release of alpha toxin causes septic
shock, while enterotoxins and TSST-1 are superantigens that may cause
toxic shock. Staphylococcal enterotoxins cause emesis (vomiting) when
ingested and the bacterium is a leading cause of food poisoning (intoxication).
The exfoliatin toxin causes scalded skin syndrome in neonates,
which results in widespread blistering and loss of the epidermis. There are
two antigenically distinct forms of the toxin, ETA and ETB. The toxins have
esterase and protease activity and apparently target a protein which is
involved in maintaining the integrity of the epidermis.
Superantigens: enterotoxins and toxic shock
S. aureus secretes two types of toxins with superantigen activity,
enterotoxins, of which there are six antigenic types (named SE-A, B, C, D, E and G),
and toxic shock syndrome toxin (TSST-1). Enterotoxins
cause diarrhea and vomiting when ingested and are responsible for
staphylococcal food poisoning. TSST-1 is expressed systemically and is the cause of
toxic shock syndrome (TSS). When expressed systemically, enterotoxins can
also cause toxic shock syndrome. In fact, enterotoxins B and C cause 50% of
non-menstrual cases of TSS. TSST-1 is weakly related to enterotoxins,
but it does not have emetic activity. TSST-1 is responsible for 75% of TSS,
including all menstrual cases. TSS can occur as a sequel to any staphylococcal
infection if an enterotoxin or TSST-1 is released systemically, and the
host lacks appropriate neutralizing antibodies.
Superantigens stimulate T cells non-specifically without normal
antigenic recognition (Figure 4). Up to one in five T cells may be activated,
whereas only 1 in 10,000 are stimulated during a usual antigen presentation.
Cytokines are released in large amounts, causing the symptoms of TSS.
Superantigens bind directly to class II major histocompatibility complexes of
antigen-presenting cells outside the conventional antigen-binding grove. This complex
recognizes only the Vb element of the T cell receptor. Thus any T cell with the
appropriate Vb element can be stimulated, whereas normally, antigen specificity is
also required in binding.
Exfoliatin toxin (ET)
The exfoliatin toxin, associated with scalded skin syndrome, causes
separation within the epidermis, between the living layers and the superficial
dead layers. The separation is through the stratum granulosum of the
epidermis. This is probably why healing occurs with little scarring although the risks
of fluid loss and secondary infections are increased. Staphylococcal
exfoliative toxin B has been shown to specifically cleave desmoglein 1, a
cadherin that is found in desmosomes in the epidermis.
Previous Page | Next Page