| dc.description.abstract | The gram-positive bacterium Staphylococcus aureus (S.aureus) is carried by up to 30% of the
population and can cause disease, including skin and soft tissue infections. But also more severe
symptoms like abscesses, sepsis and pneumonia were described. In the past, pathogenic S.aureus
strains were mainly present in hospitals. However, since the beginning of the 1990s S.aureus strains
emerged which can also be found outside of hospitals. The success of such community-associated
strains is based on a high expression of a broad variety of virulence factors including genes for
antibiotic resistance and exotoxins. Such exotoxins can be subdivided into three groups: The first
group consists of hemolysins which have the ability to lyze blood cells, namely erythrocytes,
phagocytes and lymphocytes. This effect is based on the formation of pores in the membrane of the
affected cell, which disturbs the ion metabolism and results in depletion of small molecules like ATP.
Lysis of erythrocytes could hereby help S.aureus to attain iron out of the erythrocyte-derived
proteins hemoglobin and myoglobin. Lysis of immune cells could provide a mechanism of immune
evasion, since phagocytes and lymphocytes are required for an efficient clearance of S.aureus
infections. The second group comprises the superantigens. Staphylococcal superantigens cross-link
Vβ chains of distinct T-cell receptor variants present on CD4+ T cells with major histocompatibility
complex (MHC) class II molecules of professional antigen presenting cells (APC). This cross-linking
does not require antigen specifity of the MHC class II molecules and can result in activation in up to
20% of the overall T cell population. T cell activation is followed subsequently by anergy and
depletion of the respective T cell clones, which could facilitate S.aureus infections because T cells
play an important role in clearance of bacterial infections. The third group is the group of exfoliative
toxins, which can cause proteolytic cleavage of the cadherin desmoglein-1 (Dsg1). Dsg1 is responsible
for cell-cell interactions within the skin and its cleavage results in disruption of the skin barrier. The
disruption of the skin barrier was described to be an important factor for a successful establishment
of an infection by S.aureus.
Taken together, the described staphylococcal exotoxins are important virulence factors enhancing
the ability of S.aureus to establish and maintain an infection. Although hemolysins, superantigens
and exfoliative toxins require further investigations to determine the impact of the toxins more in
detail, this knowledge could be used in the future to develop drugs and vaccines for the treatment or
prevention of S.aureus infections. | |
