Understanding the microbiome of medicinal plants

Studies in the last decades have shown that plant-microbe interactions are a key for understanding of plant growth and health, and for sustainable crop production. Moreover, secondary metabolites produced by plant-microbe interactions can have a high impact on human health and therefore are a very promising target for drug discovery. While Arabidopsis and several crops are well investigated, little is known about the role of the microbiome of medicinal plants. Therefore, pot marigold Calendula officinalis L. and chamomile Matricaria chamomilla L. will be used as model plants. They belong to the best known versatile medicinal plants and are cultivated all over the world with different chemical profiles. Asteraceae represent one of the highest developed plant families with unique ecological strategies including a diversified secondary plant metabolism. The entire plants, but especially the flowers and leaves, are characterized by a rich spectrum of biologically active metabolites, e.g. flavonoids, sesquiterpenes, and triterpenes. While the main indications for Calendula are treatment of wounds and skin diseases, chamomile preparations are commonly used for a broader spectrum of human ailments, e.g. inflammation, ulcers, wounds, spasms, and gastrointestinal disorders. In addition, both plants have become extremely popular in herbal cosmetics, however with a risk of allergy. Plant-derived medicines have been part of traditional healthcare in most parts of the world for thousands of years. While past medicinal plant research primarily focused on bioactive plant metabolites, currently, interest is shifting to compounds which are produced by associated microbes or through interaction with the host plant, because there is growing evidence that a significant number of plant metabolites is in fact produced by microbes. The overall objective of this project is to decipher structure and function of the microbial metagenome of both medicinal plants and elucidate its impact on the plants metabolome and its effects for plant and human health. The microbial biodiversity of above-ground plant parts and its genetic potential will be analyzed and associated to biologically active compounds of the metabolome of plants cultivated in Austria, California/USA and Egypt. A multi-phasic approach will be used, combining meta- omics technologies with molecular methods and analytical analyses. Results will unravel the microbiome and its impact on the plants metabolome, as well as reveal the stability of both over three different continents and their specificity in comparison to other medicinal plants. To understand the mode of action as well as for a more targeted application of the bioactive ingredients, investigations of the community composition of the human skin microflora before and after topical application of Calendula ointment will be performed. In addition to new knowledge about medicinal plant-microbe interactions, this project will open the largely untapped bioresource of the Calendula and Matricaria microbiome for its use in medicine and agriculture.

Plant-derived medicines have been part of traditional healthcare in most parts of the world for thousands of years, and secondary phytochemicals are still a highly promising target for drug discovery. Plants form close interactions with microorganisms that are essential for their performance and survival. Moreover, the plant-associated microbiome influences also the metabolic profile of the plant leading to different metabotypes, whereby a significant number of metabolites are in fact even produced by associated microbes. Microbiome analyses of different species of medicinal plants (Matricaria chamomilla L., Calendula officinalis L. and Solanum distichum Schumach. and Thonn.) revealed a plant-specific microbial colonization of their rhizosphere and phyllosphere, while the endosphere showed a more similar microbiome composition characterized by a subset of species and a significantly lower diversity. The ectophytic phyllosphere microbiome of the Asteraceae medicinal plants was dominated by Proteobacteria, Firmicutes and Actinobacteria, while the leaf endospheres were almost exclusively inhabited by Proteobacteria, among those Gammaproteobacteria were highly predominant. The flower metabolomes of the Asteraceae medicinal plants revealed a striking complexity and were highly specific for the different plant species (M. chamomilla and C. officinalis) but also for the individual sampling sites (Austria, Washington/USA and Egypt). Several individual metabolites with significant differences between samples from different sites and plant species could be identified, among them also bioactive compounds, such as the flavonoids apigenin, luteolin and quercetin. The rhizosphere communities of all investigated medicinal plants unveiled an outstandingly high microbial diversity, most notable in comparison to crop plants grown in intense agriculture. In total, 84 metagenomic bins could be recovered from the medicinal plant rhizospheres, including two nearly complete draft genomes. Sequencing the genomes of three isolated promising biocontrol candidates (Bacillus amyloliquefaciens, Paenibacillus polymyxa and Streptomyces sp.) uncovered their genotypic background for their proven direct and indirect plant growth promotion capabilities and stress resistance.