Emergence of methicillin resistance predates the clinical use of antibiotics

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

Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of 'Artocarpus heterophyllus' Lam

Colorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLC–MS–DAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 μg/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-γ) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent

Emergence of methicillin resistance predates the clinical use of antibiotics

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 antibiotics(1). 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 beta-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

Emergence of methicillin resistance predates the clinical use of antibiotics.

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

Rumors of Psychedelics, Psychotropics and Related Derivatives in Vachellia and Senegalia in Contrast with Verified Records in Australian Acacia

There are almost 1000 species of Acacia sensu stricto in Australia, while the 44 species and 4 subspecies in southern Africa were taxonomically revised in the year 2011 to Senegalia and Vachellia. There are rumors of a chemical similarity between the Australian Acacia and their southern African sister genera. Chemical analysis has unequivocally demonstrated the presence of tryptamines (i.e., DMT), β-carbolines, histamines, and phenethylamines in Australian species. However, reliable published data were not found in support of similar alkaloids in southern African (or even African) species, indicating the need for exploratory phytochemical analysis. Interestingly, the Australian species are more like the Vachellia and Senegalia from the Americas. While many reliable chemical studies have been found, there are several more that report only tentative results. Tentative data and anecdotal accounts are included in the current review to guide researchers to areas where further work can be done. For example, the current review encourages further phytochemical work to confirm if the two metabolite families, tryptamine and β-carboline alkaloids, occur together in a single specimen. Tryptamines and β-carbolines are the prerequisite ingredients of the South American psychotropic drink ayahuasca, which utilizes two different species to create this synergistic combination. These observations and others are discussed in light of geochemical variability, the potential ethnobotanical implications, and the need for further research to confirm or nullify anecdotal reports and tentative chromatographic/spectroscopic data in southern African species

Rumors of Psychedelics, Psychotropics and Related Derivatives in <i>Vachellia</i> and <i>Senegalia</i> in Contrast with Verified Records in Australian <i>Acacia</i>

There are almost 1000 species of Acacia sensu stricto in Australia, while the 44 species and 4 subspecies in southern Africa were taxonomically revised in the year 2011 to Senegalia and Vachellia. There are rumors of a chemical similarity between the Australian Acacia and their southern African sister genera. Chemical analysis has unequivocally demonstrated the presence of tryptamines (i.e., DMT), β-carbolines, histamines, and phenethylamines in Australian species. However, reliable published data were not found in support of similar alkaloids in southern African (or even African) species, indicating the need for exploratory phytochemical analysis. Interestingly, the Australian species are more like the Vachellia and Senegalia from the Americas. While many reliable chemical studies have been found, there are several more that report only tentative results. Tentative data and anecdotal accounts are included in the current review to guide researchers to areas where further work can be done. For example, the current review encourages further phytochemical work to confirm if the two metabolite families, tryptamine and β-carboline alkaloids, occur together in a single specimen. Tryptamines and β-carbolines are the prerequisite ingredients of the South American psychotropic drink ayahuasca, which utilizes two different species to create this synergistic combination. These observations and others are discussed in light of geochemical variability, the potential ethnobotanical implications, and the need for further research to confirm or nullify anecdotal reports and tentative chromatographic/spectroscopic data in southern African species

Southern Africa as a ‘cradle of incense’ in wider African aromatherapy

The modern paradigm of aromatherapy is based on in vitro assays of pure volatile organic compounds (as an essential oil), with activity at non-clinically significant concentrations. Yet traditional use of aromatic species did not involve pure essential oils because hydrodistillation was only invented in relatively recent times (estimated 1200 AD). Instead, more complex ‘full-bodied’ extracts and blends were made by following unsophisticated extraction processes resulting in mixtures of volatile organic compounds and non-volatile (fixed) metabolites. The first humans on earth were the first to experiment with aromatic medicinal plants. The close interaction between humans and aromatic plants during evolution encourages us to consider how it has informed natural selection. Modern biology has revealed a kind of specialised metabolism of natural products that recycles conjugated xenobiotics in infectious/inflammatory tissues via the secretion of β-glucuronidase. Informed by in vitro and chemical evidence, the current review narrates the philosophical argument that traditional methods of aromatic medicinal plant use in prehistoric cultures achieves tangible positive effects. What we learn from the ‘cradle of incense’ is that full-bodied extraction of aromatic medicinal plants (or aromatic exudates) can sometimes be better than hydrodistilled essential oils from the same species. This is because volatile organic compounds are more powerful when combined with other products where they act as gene expression modulators, potentiators or synergistic ingredients in deriving therapeutic outcomes

Are South African Wild Foods the Answer to Rising Rates of Cardiovascular Disease?

The rising burden of cardiovascular disease in South Africa gives impetus to managerial changes, particularly to the available foods in the market. Since there are many economically disadvantaged groups in urban societies who are at the forefront of the CVD burden, initiatives to make healthier foods available should focus on affordability in conjunction with improved phytochemical diversity to incentivize change. The modern obesogenic diet is deficient in phytochemicals that are protective against the metabolic products of sugar metabolism, i.e., inflammation, reactive oxygen species and mitochondrial fatigue, whereas traditional southern African food species have high phytochemical diversity and are also higher in soluble dietary fibres that modulate the release of sugars from starches, nurture the microbiome and produce digestive artefacts that are prophylactic against cardiovascular disease. The examples of indigenous southern African food species with high horticultural potential that can be harvested sustainably to feed a large market of consumers include: Aloe marlothii, Acanthosicyos horridus, Adansonia digitata, Aloe ferox, Amaranthus hybridus, Annesorhiza nuda, Aponogeton distachyos, Bulbine frutescens, Carpobrotus edulis, Citrullus lanatus, Dioscorea bulbifera, Dovyalis caffra, Eleusine coracana, Lagenaria siceraria, Mentha longifolia, Momordica balsamina, Pelargonium crispum, Pelargonium sidoides, Pennisetum glaucum, Plectranthus esculentus, Schinziophyton rautanenii, Sclerocarya birrea, Solenostemon rotundifolius, Talinum caffrum, Tylosema esculentum, Vigna unguiculata and Vigna subterranea. The current review explains the importance of phytochemical diversity in the human diet, it gives a lucid explanation of phytochemical groups and links the phytochemical profiles of these indigenous southern African foods to their protective effects against cardiovascular disease

High-Value Plant Species Used for the Treatment of “Fever” by the Karen Hill Tribe People

The symptom “fever” is generally not itself a terminal condition. However, it does occur with common mild to severe ailments afflicting the world population. Several allopathic medicines are available to attenuate fever by targeting the pathogen or the symptom itself. However, many people in marginal civilizations are obligated to use locally grown medicinal plants due to limited access to common pharmaceuticals. The Karen ethnic group is the biggest ethnic minority group in the hill-tribes of Thailand. They utilise a vast repertoire of medicinal plant species. Since many modern drugs were discovered out of traditional therapies, it is possible to discover new allopathic drugs in the treatment of fever and associated pathogens from the Karen people. Thus, this study aims to identify and record the ethnomedicinal plants they used for the treatment of “fever”. The names of plants used by the Thai Karen people for the treatment of fever were mined from publications on ethnomedicinal uses. Useful plant species and families were identified using the Cultural Importance Index (CI). With the mined data, 125 plant species from 52 families were identified, distributed across 25 Karen villages. A chemical cross-examination of these species provided valuable insights into chemical classes worthy of further investigation in the context of fever and associated pathogens