Beschreibung: Ascidians and their associated microbiota are prolific producers of bioactive marine natural products. Recent culture-independent studies have revealed that the tunic of the solitary ascidian Ciona intestinalis (sea vase) is colonized by a diverse bacterial community, however, the biotechnological potential of this community has remained largely unexplored. In this study, we aimed at isolating the culturable microbiota associated with the tunic of C. intestinalis collected from the North and Baltic Seas, to investigate their antimicrobial and anticancer activities, and to gain first insights into their metabolite repertoire. The tunic of the sea vase was found to harbor a rich microbial community, from which 89 bacterial and 22 fungal strains were isolated. The diversity of the tunic-associated microbiota differed from that of the ambient seawater samples, but also between sampling sites. Fungi were isolated for the first time from the tunic of Ciona. The proportion of bioactive extracts was high, since 45% of the microbial extracts inhibited the growth of human pathogenic bacteria, fungi or cancer cell lines. In a subsequent bioactivity-and metabolite profiling-based approach, seven microbial extracts were prioritized for in-depth chemical investigations. Untargeted metabolomics analyses of the selected extracts by a UPLC-MS/MS-based molecular networking approach revealed a vast chemical diversity with compounds assigned to 22 natural product families, plus many metabolites that remained unidentified. This initial study indicates that bacteria and fungi associated with the tunic of C. intestinalis represent an untapped source of putatively new marine natural products with pharmacological relevance.

Beschreibung: Massive fouling by the invasive ascidian Ciona intestinalis in Prince Edward Island (PEI, Canada) has been causing devastating losses to the local blue mussel farms. In order to gain first insights into so far unexplored factors that may contribute to the invasiveness of C. intestinalis in PEI, we undertook comparative microbiome and metabolome studies on specific tissues from C. intestinalis populations collected in invaded (PEI) and native regions (Helgoland and Kiel, Germany). Microbial community analyses and untargeted metabolomics revealed clear location- and tissue-specific patterns showing that biogeography and the sampled tissue shape the microbiome and metabolome of C. intestinalis. Moreover, we observed higher microbial and chemical diversity in C. intestinalis from PEI than in the native populations. Bacterial OTUs specific to C. intestinalis from PEI included Cyanobacteria (e.g., Leptolyngbya sp.) and Rhodobacteraceae (e.g., Roseobacter sp.), while populations from native sampling sites showed higher abundances of e.g., Firmicutes (Helgoland) and Epsilonproteobacteria (Kiel). Altogether 121 abundant metabolites were putatively annotated in the global ascidian metabolome, of which 18 were only detected in the invasive PEI population (e.g., polyketides and terpenoids), while six (e.g., sphingolipids) or none were exclusive to the native specimens from Helgoland and Kiel, respectively. Some identified bacteria and metabolites reportedly possess bioactive properties (e.g., antifouling and antibiotic) that may contribute to the overall fitness of C. intestinalis. Hence, this first study provides a basis for future studies on factors underlying the global invasiveness of Ciona species

Beschreibung: It is widely accepted that the commensal gut microbiota contributes to the health and well-being of its host. The solitary tunicate Ciona intestinalis emerges as a model organism for studying host–microbe interactions taking place in the gut, however, the potential of its gut-associated microbiota for marine biodiscovery remains unexploited. In this study, we set out to investigate the diversity, chemical space, and pharmacological potential of the gut-associated microbiota of C. intestinalis collected from the Baltic and North Seas. In a culture-based approach, we isolated 61 bacterial and 40 fungal strains affiliated to 33 different microbial genera, indicating a rich and diverse gut microbiota dominated by Gammaproteobacteria. In vitro screening of the crude microbial extracts indicated their antibacterial (64% of extracts), anticancer (22%), and/or antifungal (11%) potential. Nine microbial crude extracts were prioritized for in-depth metabolome mining by a bioactivity- and chemical diversity-based selection procedure. UPLC-MS/MS-based metabolomics combining automated (feature-based molecular networking and in silico dereplication) and manual approaches significantly improved the annotation rates. A high chemical diversity was detected where peptides and polyketides were the predominant classes. Many compounds remained unknown, including two putatively novel lipopeptides produced by a Trichoderma sp. strain. This is the first study assessing the chemical and pharmacological profile of the cultivable gut microbiota of C. intestinalis