The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics¹. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus—a notorious human pathogen—appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development.

The current text provides a comprehensive introduction to essential oils, their biosynthesis, naming, analysis, and chemistry. Importantly, this text quickly brings the reader up to a level of competence in the authentication of essential oils and their components. It gives detailed descriptions of enantiomers and other forms of stereoisomers relevant to the study of natural volatiles and essential oils. The text also describes GC-MS work and provides tips on rapid calculation of arithmetic indices, how to interpret suggested names from the NIST mass spectral library, and what additional efforts are required to validate essential oils and defeat sophisticated adulteration tactics. In brief, essential oils are mixtures of volatile organic compounds that were driven out of the raw plant material in distillation, condensed into an oil that is strongly aroma emitting, and collected in a vessel as the top layer (uncommonly bottom layer) of two phase separated liquids: oil and water. Essential oils commonly include components derived from two biosynthetic groups, being terpenes (monoterpenes, sesquiterpenes and their derivatives) and phenylpropanoids (aromatic ring with a propene tail). The current text provides details of how terpenes and phenylpropanoids are further categorised according to their parent skeleton, then recognised by the character of oxidation, which may be from oxygen, nitrogen, or sulphur, or the presence/absence of a double bond. The essential oil’s science niche is an epicentre of individuals from diverse backgrounds, such as aromatherapy, pharmacy, synthetic and analytical chemistry, or the hobbyist. To make the science more accessible to the curious student or researcher, it was necessary to write this fundamentals-level introduction to the chemistry of essential oils (i.e., organic chemistry in the context of essential oils), which is herein presented as a comprehensive and accessible overview. Lastly, the current review constitutes the only resource that highlights common errors and explains in simplistic detail how to correctly interpret GC-MS data then accurately present the respective chemical information to the wider scientific audience. Therefore, detailed study of the contents herein will equip the individual with prerequisite knowledge necessary to effectively analyse an essential oil and make qualified judgement on its authenticity.

This review is a comprehensive introduction to pertinent aspects of the extraction methodology, chemistry, analysis and pharmacology of essential oils, whilst providing a background of general organic chemistry concepts to readers from non-chemistry oriented backgrounds. Furthermore, it describes the historical aspects of essential oil research whilst exploring contentious issues of terminology. This follows with an examination of essential oil producing plants in the Australian context with particular attention to Aboriginal custom use, historical successes and contemporary commercial prospects. Due to the harsh dry environment of the Australian landmass, particularly to the cyclical climatic variation attendant upon repeated glaciation/post-glaciation cycles, the arid regions have evolved a rich assortment of unique endemic essential oil yielding plants. Though some of these aromatic plants (particularly myrtaceous species) have given birth to commercially valuable industries, much remains to be discovered. Given the market potential, it is likely that recent discoveries in our laboratory and elsewhere will lead to new product development. This review concludes with an emphasis on the use of chemotaxonomy in selection of commercially viable cultivar chemotypes from the Australian continent. Finally, drawing largely from our own results we propose a list of Australian endemic species with novel commercial potential.

The new era of multidrug resistance of pathogens against frontline antibiotics has compromised the immense therapeutic gains of the ‘golden age,’ stimulating a resurgence in antimicrobial research focused on antimicrobial and immunomodulatory components of botanical, fungal or microbial origin. While much valuable information has been amassed on the potency of crude extracts and, indeed, purified compounds there are too many reports that uncritically extrapolate observed in vitro activity to presumed ingestive and/or topical therapeutic value, particularly in the discipline of ethnopharmacology. Thus, natural product researchers would benefit from a basic pharmacokinetic and pharmacodynamic understanding. Furthermore, therapeutic success of complex mixtures or single components derived therefrom is not always proportionate to their MIC values, since immunomodulation can be the dominant mechanism of action. Researchers often fail to acknowledge this, particularly when ‘null’ activity is observed. In this review we introduce the most up to date theories of oral and topical bioavailability including the metabolic processes affecting xenobiotic biotransformation before and after drugs reach the site of their action in the body. We briefly examine the common methodologies employed in antimicrobial, immunomodulatory and pharmacokinetic research. Importantly, we emphasize the contribution of synergies and/or antagonisms in complex mixtures as they affect absorptive processes in the body and sometimes potentiate activity. Strictly in the context of natural product research, it is important to acknowledge the potential for chemotypic variation within important medicinal plants. Furthermore, polar head space and rotatable bonds give a priori indications of the likelihood of bioavailability of active metabolites. Considering this and other relatively simple chemical insights, we hope to provide the basis for a more rigorous scientific assessment, enabling researchers to predict the likelihood that observed in vitro anti-infective activity will translate to in vivo outcomes in a therapeutic context. We give worked examples of tentative pharmacokinetic assessment of some well-known medicinal plants.

Grape seeds are a rich source of flavan-3-ol monomers, oligomers, and polymers. The diverse profile of compounds includes mainly B-type procyanidins (especially C4→C8 linked molecules) and the key monomers, catechin, and epicatechin that are positively implicated in the ‘French Paradox’. Today grape seed nutraceuticals have become a multi-million-dollar industry. This has created incentives to elucidate the variations in chemistry across cultivars, to identify signs of adulteration, and to understand the intrinsic and extrinsic factors controlling the expression of metabolites in the seeds’ metabolome. This review provides a critical overview of the existing literature on grape seed chemistry. Although the biosynthetic pathways for polymeric procyanidins in seeds have not yet been explained, abiotic factors have been shown to modulate associated genes. Research of extrinsic factors has demonstrated that the control of procyanidin expression is strongly influenced, in order of importance, by genotype (species first, then variety) and environment, as claimed anecdotally. Unfortunately, research outcomes on the effects of abiotic factors have low certainty, because effects can be specific to genotype or variety, and there is limited control over physical metrics in the field. Thus, to gain a fuller understanding of the effects of abiotic factors and biosynthetic pathways, and realise potential for optimisation, a more fundamental research approach is needed. Nevertheless, the current synthesis offers insight into the selection of species or varieties according to the profile of polyphenols, as well as for optimisation of horticultural practices, with a view to produce products that contain the compounds that support health claims.

This commentary critically examines the modern paradigm of natural volatiles in ‘medical aromatherapy’, first by explaining the semantics of natural volatiles in health, then by addressing chemophenetic challenges to authenticity or reproducibility, and finally by elaborating on pharmacokinetic and pharmacodynamic processes in food, therapy, and disease prophylaxis. Research over the last 50 years has generated substantial knowledge of the chemical diversity of volatiles, and their strengths and weaknesses as antimicrobial agents. However, due to modest in vitro outcomes, the emphasis has shifted toward the ability to synergise or potentiate non-volatile natural or pharmaceutical drugs, and to modulate gene expression by binding to the lipophilic domain of mammalian cell receptors. Because essential oils and natural volatiles are small and lipophilic, they demonstrate high skin penetrating abilities when suitably encapsulated, or if derived from a dietary item they bioaccumulate in fatty tissues in the body. In the skin or body, they may synergise or drive de novo therapeutic outcomes that range from anti-inflammatory effects through to insulin sensitisation, dermal rejuvenation, keratinocyte migration, upregulation of hair follicle bulb stem cells or complementation of anti-cancer therapies. Taking all this into consideration, volatile organic compounds should be examined as candidates for prophylaxis of cardiovascular disease. Considering the modern understanding of biology, the science of natural volatiles may need to be revisited in the context of health and nutrition.