Staphylococcal Exfoliative Toxin Induces Caseinolytic Activity

Purification of Protease from a Mixture of Exfoliative Toxin and Newborn-Mouse Epidermis

“…We reported that casein-hydrolyzing activity appeared in a mixture of ET and newborn-mouse epidermis (17). As other authors have noted, this suggests that the epidermal splitting seen in SSSS is caused by a protease.…”

Staphylococcal scalded skin syndrome

“…Immunocytochemical studies have shown that the toxin binds to the filaggrin group of proteins in keratohyalin granules,14and because filaggrins act as intracellular anchors of desmosomes, many investigators have speculated that epidermal splitting is a result of rupture of these desmosomes, probably from proteolytic activity of the toxins 15-17. The toxins in their native form, however, do not have any significant proteolytic activity,18 19 and the hypothesis that they may be serine proteases comes from indirect evidence: (1) both toxins show significant sequence homology with the staphylococcal V8 protease, particularly in the region of the serine–aspartic acid–histidine catalytic triad that forms the active site of trypsin-like serine proteases15 ; (2) replacing any of the three amino acids that form the catalytic triad of the toxins results in complete loss of biological activity when injected into newborn mice16 17 19; (3) incubation of ETA with neonatal mouse epidermis18 or neonatal mouse epidermal extract19 results in the induction of caseinolytic activity in the supernatant; and (4) recent computer modelling 20 and crystallographic studies21 22on the three dimensional structure of the toxins have revealed a high degree of structural similarity with known glutamate specific trypsin-like serine proteases. Deletion studies have shown that the highly charged amino terminal of the exfoliative toxins is essential for their activity,22 and recent structural studies have led to speculation that this region may be responsible for binding an epidermal receptor, which in turn may result in a conformational change that exposes the toxin’s active catalytic site 21…”

“…However, research using the neonatal mouse epidermis assay18 19 could be extended to investigate whether the exfoliative toxins are indeed serine proteases and whether they bind to any receptors,44 and to elucidate events following binding. The model could also be used to determine any changes occurring in ETA, including a conformational change after receptor binding to expose the active catalytic site, as has recently been speculated from structural models 21…”

Staphylococcal scalded skin syndrome

“…'l However, addition of protease inhibitors to both in-vitro and in-vivo models of epidermolysis failed to inhibit epidermal splitting". [53][54][55] and, until the demonstration of similarities between ET and serine protease (see below), it was agreed generally that ET had no proteolytic activity.…”