superantigens play an important role in the natural course of atopic dermatitis [18
]. Previous studies have focused on only a few superantigens produced by S. aureus
strains obtained from patients with atopic dermatitis. The present study is the most comprehensive study of superantigens in patients with atopic dermatitis, examining all well-characterized superantigens except SEl-P, which is an uncommon superantigen.
Several important observations were made. First, the S. aureus
strains from patients with steroid-resistant atopic dermatitis showed the ability to produce large numbers of super-antigen types per organism, significantly higher than those produced by other skin isolates (group 3 isolates from a general population with atopic dermatitis) and by mucous membrane isolates (group 2 vaginal isolates). Each superantigen is known to activate only a subset of T cells expressing particular Vb-TCR regions [15
]. The net effect of S. aureus
strains producing a larger number of superantigens types would be to recruit larger numbers of T cells to produce proinflammatory cytokines and to induce a wider spectrum of T cells that fail to respond to the immunosuppressive effects of corticosteroids. This process could thus contribute to steroid-resistant atopic dermatitis.
Second, our studies suggest that the S. aureus isolates from patients with steroid-resistant atopic dermatitis have been selected for their production of greater numbers of superantigens than those produced by isolates from a general population of patients with atopic dermatitis and by vaginal isolates from normal healthy women. Although the cause of this selection is unknown, the use of steroids to manage atopic dermatitis, with the intent to reduce inflammation and consequent skin damage, would typically create cutaneous environments that reduce S. aureus colonization. Increased superantigen production by individual organisms may be necessary to promote skin inflammation and continued staphylococcal infection in patients with atopic dermatitis. Alternatively, the antimicrobial treatment approaches, including antibiotic treatment, used for management of atopic dermatitis should be investigated to determine their selection bias for such strains of S. aureus.
Third, in addition to having the potential to make more types of superantigens, S. aureus
isolates from patients with steroid-resistant atopic dermatitis also have dysregulated production of superantigens and produce unusual combinations of superantigens. For example, it is commonly assumed that S. aureus
strains cannot produce the superantigens TSST-1 and SEB together, possibly because the pathogenicity islands that encode the toxins may occupy the same chromosomal position [30
]. This is clearly not the case, because several isolates from patients with steroid-resistant atopic dermatitis coproduced both superantigens. In addition, superantigen production is strictly under the control of the global regulator SrrA-SrrB [12
]. This 2-component system functions as a repressor of exotoxin production by S. aureus
under low-oxygen conditions. Its repressive effects are lost in the presence of 12% oxygen [36
]. Thus, no superantigens are produced by S. aureus
under anaerobic conditions, despite the organism's ability to grow anaerobically. We observed that 2 of 6 S. aureus
isolates had truncated genes for SrrA-SrrB. These strains are able to produce superantigens, even under unfavorable, low-oxygen conditions [28
]. We showed that S. aureus
isolates from patients with steroid-resistant atopic dermatitis are more likely than other S. aureus
isolates to produce the superantigens typically made in high concentrations, such as TSST-1, SEB, and SEC. In addition, the organisms produce SEA in the postexponential phase (when bacterial cell densities are high) rather than in the exponential phase [10
], giving these organisms the ability to make higher concentrations of this superantigen than would be expected. Finally, our studies show that production of superantigens, such as the enterotoxin gene cluster [29
] of proteins (SEl-G, SEl-M, SEl-N, SEl-O, and SEI), has been altered. In many strains, these superantigens are no longer linked on a single pathogenicity island.
Collectively, the present study suggests that S. aureus
isolates from patients with steroid-resistant atopic dermatitis are being selected for their greater capability to produce superantigens. These proteins are critical virulence factors for S. aureus
strains. The data suggest that the spread of such strains to other humans may predict their causation of additional illnesses. For example, a TSST-1–positive strain, without a functional SrrA-SrrB system, could cause menstrual, vaginal TSS without regard to the oxygen content of the vagina. It has been hypothesized that the association of tampons with TSS is related to their oxygenation of a typically anaerobic environment [37
]. In individuals with TSST-1–positive strains, TSS may occur in the absence of tampon use.