Antibiotic peptides are important effector molecules in host-parasite interactions throughout the living world. In vertebrates, they function in first-line host defense by antagonizing a wide range of microbes including bacteria, fungi, and enveloped viruses. The antibiotic activity is thought to be based on their cationic, amphipathic nature, which enables the peptides to impair vital membrane functions. Molecular details for such activities have been elaborated with model membranes; however, there is increasing evidence that these models may not reflect the complex processes involved in the killing of microbes. For example, the overall killing activity of the bacterial peptide antibiotic nisin is composed of independent activities such as the formation of target-mediated pores, inhibition of cell-wall biosynthesis, formation of nontargeted pores, and induction of autolysis. We studied the molecular modes of action of human defense peptides and tried to determine whether they impair membrane functions primarily and whether additional antibiotic activities may be found. We compared killing kinetics, solute efflux kinetics, membrane-depolarization assays, and macromolecular biosynthesis assays and used several strains of Gram-positive cocci as test strains. We found that membrane depolarization contributes to rapid killing of a significant fraction of target cells within a bacterial culture. However, substantial subpopulations appear to survive the primary effects on the membrane. Depending on individual strains and species and peptide concentrations, such subpopulations may resume growth or be killed through additional activities of the peptides. Such activities can include the activation of cell-wall lytic enzymes, which appears of particular importance for killing of staphylococcal strains.

Atopic dermatitis is a chronic inflammatory skin disease with a high incidence in school children and adults. Disease pathogenesis is complex and the background is multifactorial, making the underlying predispositions elusive. Understanding new pathogenic pathways may lead to the development of new drugs with enhanced benefit for the patient.

Skin colonization with Staphylococcus aureus is often associated with atopic dermatitis, and staphylococcal enterotoxins have been implicated in the etiology of atopic disease. In this study, the colonization of patients with atopic dermatitis and their parents was investigated in order to evaluate the possibility of intrafamiliar transmission. S. aureus strains were isolated from 30 of 45 patients (66%). In 19 of 29 families (65%), at least one parent carried S. aureus, and the overall colonization rate of the parents was 48%. All strains were typed by pulsed-field gel electrophoresis (PFGE), and the presence of enterotoxin genes in the strains was assayed by multiplex PCR. A high percentage (84%) of the isolates present on the children and on at least one of their parents displayed identical PFGE and enterotoxin patterns as well as identical antibiotic resistance profiles, indicating intrafamiliar transmission. Forty-five percent of the strains did not carry any enterotoxin gene. The most frequently found enterotoxin genes were seg and sei, which were present in 36% of the strains, and seb, which was found in 24% of the strains. The other toxin genes occurred only in low frequencies. Most strains were resistant to penicillin (82%), and 15% showed resistance to more than one antibiotic. Intermediatelyvancomycin-resistant S. aureus or methicillin-resistant S. aureus strains were not detected. In conclusion, this study indicates that the colonization rate of parents of atopic children is rather high and may increase the risk of recolonization of the child.Staphylococcus aureus is a gram-positive pathogen that has been implicated in the pathogenesis of atopic dermatitis (AD). AD is one of the most frequent chronic inflammatory skin diseases and is found in 10% of all German children starting school (35). It is characterized by a dysregulation of the immune system that involves an increased Th2 response with an enhanced level of Th2 cytokines in the acute phase, a decreased level of other cytokines (e.g., tumor necrosis factor alpha), and decreased production of antistaphylococcal peptides of the innate immune system, i.e., ␤-defensin 3 and cathelicidins (12,30). This peptide deficiency, the impaired skin integrity, and the increased expression of fibrinogen (9) favor colonization with S. aureus in AD, which is found in a higher percentage on the skin of affected children than on the skin of a healthy control group (23). Many strains of S. aureus are able to secrete superantigens, i.e., enterotoxins and toxic shock syndrome toxin. The production of superantigens may lead to an aggravation of AD (3), and a reduction of colonization has been shown to be effective in reducing the severity of the disease (14). Furthermore, exposure to superantigens may lead to the sensitization of the patient and the production of specific immunoglobulin E antibodies against enterotoxin A and enterotoxin B. These antibody titers were found to be elevated in patients with severe skin lesions (17,25). Therefore, a reduction of S. aureus ...

We developed a new model for the study of human Tip-DC and provide the first evidence of their pro-inflammatory capacity.