The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data.

The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S.aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S.aureus. The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis. These AMPs were strain-specific, highly potent, selectively killed S.aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S.aureus. These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.

The human skin is an organ with a surface area of 1.5-2 m 2 that provides our interface with the environment. The molecular composition of this organ is derived from host cells, microbiota, and external molecules. The chemical makeup of the skin surface is largely undefined. Here we advance the technologies needed to explore the topographical distribution of skin molecules, using 3D mapping of mass spectrometry data and microbial 16S rRNA amplicon sequences. Our 3D maps reveal that the molecular composition of skin has diverse distributions and that the composition is defined not only by skin cells and microbes but also by our daily routines, including the application of hygiene products. The technological development of these maps lays a foundation for studying the spatial relationships of human skin with hygiene, the microbiota, and environment, with potential for developing predictive models of skin phenotypes tailored to individual health.human skin | 3D mapping | mass spectrometry | 16S rRNA T he skin provides the interface between our internal molecular processes and the external environment. The stratum corneum (SC), the outer layer of the epidermis, is the most exposed organ of the human body and is composed of molecules derived from our own skin cells, our microbiota, and the environment (1). In addition, it may be possible that personal hygiene products, the clothing we wear, and the food we eat can affect the chemical composition of the skin (2, 3). The chemical environment of the skin is also critical for the development of microbial communities, yet there are no systematic workflows that can be used to correlate skin chemistry and microbes. Human skin microbiome inventories are changing our views of commensal organisms and their roles in establishing and maintaining the immune system and general epithelial health (4-7), but their role in biotransformation of skin molecules is as yet poorly characterized.Understanding the molecular topography of the surface of the SC will provide insights into the chemical environment in which microbes reside on the skin and how in turn they modify this environment. To understand the relationship between the chemical milieu and the microbial communities, we must develop workflows that map the chemistry and microbiology of the human skin and that determine the associations between them. The composition of the human skin microbiota has been correlated with skin anatomy, dividing into moist, dry, and sebaceous microenvironments, and can be influenced by beauty and hygiene products (2-9). Regions such as the face, chest, and back, areas with a high density of sebaceous glands, promote growth of lipophilic microorganisms such as Propionibacterium and Malassezia. In contrast, less exposed regions, such as the groin, axilla, and toe web, which are higher in temperature and moisture content, are colonized by Staphylococcus and Corynebacterium (7, 10, 11). Previous studies have reported mass spectrometry (MS) methods to identify compounds from human skin (12, 13). However, th...