Staphylococcus epidermidis Isolated From Newborn Infants Express Pilus-Like Structures and Are Inhibited by the Cathelicidin-Derived Antimicrobial Peptide LL37

Abstract

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...

Cathelicidin-like Helminth Defence Molecules (HDMs): Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

“…The inactivity of LL-37 against S. aureus and S. epidermis is consistent with other studies [64]. However, the anti-microbial effect of LL-37 on Staphylococcus could be strain dependent as several studies have reported an effect of this peptide on both S epidermis [65] and S. aureus [66], [67]. Despite structural similarities with the mammalian peptides tested, none of the HDMs demonstrated bactericidal activity against any species of bacteria at the concentrations tested (<0.25 to 128 µg/ml).…”

Human cathelicidin peptide LL37 inhibits both attachment capability and biofilm formation ofStaphylococcus epidermidis

“…Staphylococcus epidermidis ATCC35984 strain did not produce biofilm in BM2 minimal medium (Overhage et al. 2008), and LL37 did not inhibit biofilm formation in combined MHB (Mueller Hinton Broth; Nelson et al. 2009), in our hands.…”

“…Peptide LL37 was purchased from Innovagen (Lund, Sweden). Distilled water contained 0·05% acetic acid was used for the dilutions of LL37 to prevent the precipitation of the peptide (Nelson et al. 2009).…”

Electron microscopy of Staphylococcus epidermidis fibril and biofilm formation using image-enhancing ionic liquid

“…Moreover, it was reported that Aap is fibrillar adhesion [15]. Nelson et.al reported that fibrinogenbinding protein Fbe and accumulation-associated protein Aap play major roles in the adherence of cells to accumulative growth on the polymer surface [14].…”

“…Especially, Staphylococcus epidermidis is well known as a commensal microorganism of human skin, nares, and mucous membranes [12,13]. Although fibrillar structures of S. epidermidis have been observed [11,14,15], observations of the ultrastructure of fibrils and detailed information on biofilm formation have not been reported till date.…”