Exploring the human hair follicle microbiome.

Human hair follicles (HFs) carry complex microbial communities that differ from the skin surface microbiota. This likely reflects that the HF epithelium differs from the epidermal barrier in that it provides a moist, less acidic, and relatively ultraviolet light-protected environment, part of which is immune-privileged, thus facilitating microbial survival. Here we review the current understanding of the human HF microbiome and its potential physiological and pathological functions, including in folliculitis, acne vulgaris, hidradenitis suppurativa, alopecia areata and cicatricial alopecias. While reviewing the main human HF bacteria (such as Propionibacteria, Corynebacteria, Staphylococci and Streptococci), viruses, fungi and parasites as human HF microbiome constituents, we advocate a broad view of the HF as an integral part of the human holobiont. Specifically, we explore how the human HF may manage its microbiome via the regulated production of antimicrobial peptides (such as cathelicidin, psoriasin, RNAse7 and dermcidin) by HF keratinocytes, how the microbiome may impact on cytokine and chemokine release from the HF, and examine hair growth-modulatory effects of antibiotics, and ask whether the microbiome affects hair growth in turn. We highlight major open questions and potential novel approaches to the management of hair diseases by targeting the HF microbiome.

AmAMP1 from Acropora millepora and damicornin define a family of coral-specific antimicrobial peptides related to the Shk toxins of sea anemones.

A candidate antimicrobial peptide (AmAMP1) was identified by searching the whole genome sequence of Acropora millepora for short (<125AA) cysteine-rich predicted proteins with an N-terminal signal peptide but lacking clear homologs in the SwissProt database. It resembled but was not closely related to damicornin, the only other known AMP from a coral, and was shown to be active against both Gram-negative and Gram-positive bacteria. These proteins define a family of AMPs present in corals and their close relatives, the Corallimorpharia, and are synthesised as preproproteins in which the C-terminal mature peptide contains a conserved arrangement of six cysteine residues. Consistent with the idea of a common origin for AMPs and toxins, this Cys motif is shared between the coral AMPs and the Shk neurotoxins of sea anemones. AmAMP1 is expressed at late stages of coral development, in ectodermal cells that resemble the "ganglion neurons" of Hydra, in which it has recently been demonstrated that a distinct AMP known as NDA-1 is expressed.

Control of foot differentiation in Hydra: phylogenetic footprinting indicates interaction of head, bud and foot patterning systems.

Homeodomain transcription factor CnNK-2 seems to play a major role in foot formation in Hydra. Recently, we reported in vitro evidence indicating that CnNK-2 has autoregulatory features and regulates expression of the morphogenetic peptide pedibin. We proposed that CnNK-2 and pedibin synergistically orchestrate foot differentiation processes. Here, we further analyzed the regulatory network controlling foot formation in Hydra. By phylogenetic footprinting we compared the CnNK-2 5'-flanking sequence from two closely related species, Hydra vulgaris and Hydra oligactis. Unexpectedly, we detected a highly conserved binding site for HNF-3beta, a vertebrate Forkhead transcription factor, in the CnNK-2 5'-flanking region. The Hydra HNF-3beta homolog budhead is predominantly expressed in the apical region of the body column and early during budding. Budhead is absent from tissue expressing CnNK-2 and thought to be involved in determining tissue for head differentiation. By electrophoretic mobility shift assays we demonstrate an in vitro interaction between recombinant budhead protein and the interspecific conserved HNF-3beta binding motif in the CnNK-2 5'-flanking region. Our results strengthen the view of CnNK-2 as an important regulator during foot patterning processes. Furtheron, they point to budhead as a candidate for a transcriptional regulator of CnNK-2 and to an interaction of foot and head patterning processes in Hydra on the molecular level.

Control of foot differentiation in Hydra: in vitro evidence that the NK-2 homeobox factor CnNK-2 autoregulates its own expression and uses pedibin as target gene.

The foot of the simple metazoan Hydra is a highly dynamic body region of constant tissue movement, cell proliferation, determination and differentiation. Previously, two genes have been shown to participate in the development and differentiation of this body region: homeodomain factor CnNK-2 and signal peptide pedibin [Dev. Biol. 180 (1996) 473; Development 126 (1999) 517; Development 122 (1996) 1941; Mech. Dev. 106 (2001) 37]. CnNk-2 functions as transcriptional regulator and is responsive to changes in the positional value while the secreted peptide pedibin serves as "extrinsic" positional signal. Exposure of polyps to pedibin increases the spatial domain of CnNK-2 expression towards the gastric region, indicating that positional signals are integrated at the cis-regulatory region of CnNK-2. In the present study, to elucidate the molecular basis of the interaction of CnNK-2 and pedibin, we characterized the 5' regulatory regions of both genes. Within the CnNK-2 5' upstream region, electrophoretic mobility shift assays showed that putative NK-2 binding motifs are specifically bound by both nuclear protein from Hydra foot and by recombinant CnNK-2, suggesting that CnNK-2 might autoregulate its own expression. This is the first indication for an autoregulatory circuit in Hydra. In addition, we also identified NK-2 binding sites in the cis-regulatory region of the pedibin gene, indicating that this gene is one of the targets of the transcription factor CnNK-2. On the basis of these results, we present a model for the regulatory interactions required for patterning the basal end of the single axis in Hydra which postulates that CnNK-2 together with pedibin orchestrates foot specific differentiation.