Toxin Levels in Serum Correlate with the Development of Staphylococcal Scalded Skin Syndrome in a Murine Model

Abstract

Staphylococcal scalded skin syndrome (SSSS) is an exfoliative dermatitis that results from infection with exfoliative toxin-producing Staphylococcus aureus. SSSS is seen primarily in infants and children. Here we ask if there is a specific maturation process that protects healthy adults from this syndrome. For these studies, an active recombinant exfoliative toxin A (rETA) was used in a neonatal mouse model. A time course generated on the susceptibility to the toxin as a function of mouse age indicated that BALB/c mice developed the characteristic symptoms of SSSS until day 7 of life. Between day 7 and day 8 of life there was a dramatic decrease in susceptibility, such that mice at day 9 of life were resistant to the effects of the toxin. This time course corresponds approximately to the time needed for maturation of the adaptive immune response, and SSSS in adults is often identified with immunocompromised states. Therefore, mice deficient in this response were examined. Adult mice thymectomized at birth and adult SCID mice did not develop the symptoms of SSSS after injection with the toxin, indicating that the adaptive immune response is not responsible for the lack of susceptibility observed in the older mice. SSSS in adults is also associated with renal disorders, suggesting that levels of toxin in serum are important in the development of the disease. rETA was not cleared as efficiently from the serum of 1-day-old mice compared to clearance from 10-day-old mice. Ten-day-old mice were given repeated injections of toxin so that the maximal level of toxin was maintained for a sustained period of time, and exfoliation occurred in these mice. Thus, whereas the adaptive immune response is not needed for protection of adult mice from SSSS, efficient clearance of the toxin from the bloodstream is a critical factor.Staphylococcal scalded skin syndrome (SSSS) is an exfoliative dermatitis characterized by the formation of large bullae and separation of extended areas of the epidermis (for a recent review see reference 10). SSSS results from infection with exfoliative toxin A (ETA) or exfoliative toxin B (ETB) producing Staphylococcus aureus (4, 12) and is primarily a disease of infants and children (7,9). In children, the syndrome is associated with a trivial infective focus, 3% mortality with appropriate antibiotic therapy, and infrequent bacteremia (9). In contrast, the syndrome in adults is usually associated with significant bacteremia and a 50% mortality rate even with appropriate antibiotic therapy. SSSS in adults is associated with immunocompromised states, renal deficiencies, diabetes mellitus, and old age (7).In 1970, Melish et al. (12) demonstrated that a mouse less than 5 days old exfoliated after injection with exfoliative toxin producing S. aureus, while mice more than 7 days old did not exfoliate. This information, along with the clinical observation that SSSS is usually seen in children and only rarely in adults, led us to ask if there is a specific maturation process protecting adults from the action ...

Staphylococcal scalded skin syndrome related to an exfoliative toxin A- and B-producing strain in preterm infants

“…Relatively low antibody titres, as generally seen in premature infants, are mentioned in the literature as potential contributing factors [12,13]. In the light of a more recent publication, immature clearance of the toxin from the bloodstream seems to be a much more likely explanation for this occurrence [15]. This entity in its generalised form is the most severe manifestation of all S. aureus associated skin diseases.…”

“…The presence of ETA was confirmed by Western blot analysis using anti-ETA polyclonal antiserum. Toxin activity was confirmed by injection of 10 ll of the partially purified culture supernantant into the subcutaneous tissue at the nape of the neck of newborn Balb/c mice as described [14,15]. The mice were placed back with lactating mothers and were observed at 4 h post-injection for signs of exfoliation.…”

“…PCR amplifications were performed using Taq DNA polymerase (Bethesda Research Laboratories, Gaithersburg Md.) under standard conditions [15]. The strains isolated from the first patient were positive for the genes encoding ETA and ETB.…”

Clinical Manifestations of Staphylococcal Scalded-Skin Syndrome Depend on Serotypes of Exfoliative Toxins

“…This link between ETB and generalized SSSS might be due to increased virulence of ETB or to more abundant ETB release. Plano et al recently demonstrated in an experimental model that high ET serum concentrations were associated with generalized SSSS (21). Differential passage of ETA and ETB through the epithelium could also contribute to this link between ETB and generalized SSSS.…”

Sensitive and Specific Detection of Staphylococcal Epidermolysins A and B in Broth Cultures by Flow Cytometry-Assisted Multiplex Immunoassay

“…Thus, it is important to distinguish between streptococci and staphylococci for diagnosis and further to deter- To date, PCR-assisted detection of epidermolysin-encoding genes has been reported only after isolation of staphylococci (3,4,14,17). Injected epidermolysins have been shown to persist in serum in mice (25), as have epidermolysin-producing isolates from patients with atopic dermatitis (29). The ability to detect these toxins directly in bulla fluids and possibly in sera might be of interest.…”