Coagulase-negative staphylococci and its subtype Staphylococcus epidermidis are major indigenous Gram-positive inhabitants of the human skin. Colonization occurs in direct connection with birth and terrestrial adaptation. This study focuses on factors that may influence skin colonization of the newborn infant that relates to the immune status of both the bacteria and the host. Skin is an effective barrier against bacteria, and this function is partly mediated by the presence of antimicrobial peptides including human cathelicidin peptide LL37. Gram-positive bacteria have been described to have adhesive pili on their surface that mediates specific attachment to the host. Here, we identify, by negative staining transmission electron microscopy (EM), two different types of piluslike structures commonly expressed on S. epidermidis isolated from newborn infants. We also show that the cathelicidin antimicrobial peptide LL37, constitutively expressed in the skin barrier of the newborn, significantly inhibited growth of S. epidermidis indicating its importance for the ecological stability of the skin microbiota. Further studies are required to elucidate molecular mechanisms of host-microbe interactions, both for the maintenance of a mutually beneficial homeostatic relationship and for the protection of self when it results in overt disease. (Pediatr Res 66: 174-178, 2009) C oagulase-negative staphylococci (CoNS) are major skin commensals in humans (1). Within the first few hours of life colonization occurs (2), and by 1 d of age 84% of all healthy neonates have their skin colonized (3). Among the CoNS, particular attention has been focused on Staphylococcus epidermidis because it is the most common species responsible for infection causing significant morbidity, mortality, and incurring healthcare costs worldwide (4). In neonates, CoNS have emerged as prevalent and important pathogens, responsible for approximately 50% of all episodes of lateonset (Ͼ72 h) sepsis in very low birth weight infants (5). Recent evidence also links these bacteria to the pathogenesis of the immunologic skin reaction erythema toxicum, frequently seen in healthy newborns (3).Ecological stability of the commensal microflora is partly maintained by interactions with its human host. Our knowledge of how commensal bacteria interact with their host or how they communicate with each other is limited. We know that at birth commensals have to face the antimicrobial defense mechanisms of the skin and the vernix caseosa, a cream-like coating on newborns secreted by the fetal sebaceous glands. Human antimicrobial cathelicidin peptide LL37 is present in both vernix caseosa and the skin already at the time of birth, and the peptide is also up-regulated in the erythema toxicum lesions of the newborn infant (6). The presence of LL37 offers increased protection against bacterial infections in mice and humans (7,8). Thus, we hypothesized that LL37 is of importance for the microbial milieu of the skin, and we tested if it could influence growth of S. epi...