Highlighting the biotechnological potential of deep oceanic crust fungi through the prism of their antimicrobial activity

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Quemener, M., Dayras, M., Frotté, N., Debaets, S., Le Meur, C., Barbier, G., Edgcomb, V., Mehiri, M., & Burgaud, G. Highlighting the biotechnological potential of deep oceanic crust fungi through the prism of their antimicrobial activity. Marine Drugs, 19(8), (2021): 411, https://doi.org/10.3390/md19080411.Among the different tools to address the antibiotic resistance crisis, bioprospecting in complex uncharted habitats to detect novel microorganisms putatively producing original antimicrobial compounds can definitely increase the current therapeutic arsenal of antibiotics. Fungi from numerous habitats have been widely screened for their ability to express specific biosynthetic gene clusters (BGCs) involved in the synthesis of antimicrobial compounds. Here, a collection of unique 75 deep oceanic crust fungi was screened to evaluate their biotechnological potential through the prism of their antimicrobial activity using a polyphasic approach. After a first genetic screening to detect specific BGCs, a second step consisted of an antimicrobial screening that tested the most promising isolates against 11 microbial targets. Here, 12 fungal isolates showed at least one antibacterial and/or antifungal activity (static or lytic) against human pathogens. This analysis also revealed that Staphylococcus aureus ATCC 25923 and Enterococcus faecalis CIP A 186 were the most impacted, followed by Pseudomonas aeruginosa ATCC 27853. A specific focus on three fungal isolates allowed us to detect interesting activity of crude extracts against multidrug-resistant Staphylococcus aureus. Finally, complementary mass spectrometry (MS)-based molecular networking analyses were performed to putatively assign the fungal metabolites and raise hypotheses to link them to the observed antimicrobial activities.This study was funded by National Science Foundation grants OCE-1658031 to Virginia Edgcomb. Fungal isolates were obtained from the Université de Bretagne Occidentale Culture Collection (UBOCC, Plouzané, France, www.univ-brest.fr/ubocc, accessed date in July 2021) and AmelieWeill is acknowledged here as head of the UBOCC

Marine anticancer agents: An overview with a particular focus on their chemical classes

UID/Multi/04378/2019 IF/00700/2014 grant number 216Z167 grant RTA 2015-00010-C03-02 No. PBA/MB/16/01 PDOC/19/02/01The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.publishersversionpublishe

A New Hydroxylated Nonaprenylhydroquinone from the Mediterranean Marine Sponge Sarcotragus spinosulus

Chemical investigation of the Mediterranean sponge Sarcotragus spinosulus led to the isolation of a new hydroxylated nonaprenylhydroquinone, along with two known metabolites, hepta- and octaprenylhydroquinones. The structure of the new metabolite was assigned by extensive 1D and 2D NMR analyses and MS studies. The antileukemic effect of the three compounds towards the chronic myelogenous leukemia (CML) cells line K562 was also evaluated

Recent progress in marine mycological research in different countries, and prospects for future developments worldwide

Early research on marine fungi was mostly descriptive, with an emphasis on their diversity and taxonomy, especially of those collected at rocky shores on seaweeds and driftwood. Subsequently, further substrata (e.g. salt marsh grasses, marine animals, seagrasses, sea foam, seawater, sediment) and habitats (coral reefs, deep-sea, hydrothermal vents, mangroves, sandy beaches, salt marshes) were explored for marine fungi. In parallel, research areas have broadened from micro-morphology to ultrastructure, ecophysiology, molecular phylogenetics, biogeography, biodeterioration, biodegradation, bioprospecting, genomics, proteomics, transcriptomics and metabolomics. Although marine fungi only constitute a small fraction of the global mycota, new species of marine fungi continue to be described from new hosts/substrata of unexplored locations/habitats, and novel bioactive metabolites have been discovered in the last two decades, warranting a greater collaborative research effort. Marine fungi of Africa, the Americas and Australasia are under-explored, while marine Chytridiomycota and allied taxa, fungi associated with marine animals, the functional roles of fungi in the sea, and the impacts of climate change on marine fungi are some of the topics needing more attention. In this article, currently active marine mycologists from different countries have written on the history and current state of marine fungal research in individual countries highlighting their strength in the subject, and this represents a first step towards a collaborative inter- and transdisciplinary research strategy

Inhibition of Bacterial and Fungal Biofilm Formation by 675 Extracts from Microalgae and Cyanobacteria

Bacterial biofilms are complex biological systems that are difficult to eradicate at a medical, industrial, or environmental level. Biofilms confer bacteria protection against external factors and antimicrobial treatments. Taking into account that about 80% of human infections are caused by bacterial biofilms, the eradication of these structures is a great priority. Biofilms are resistant to old-generation antibiotics, which has led to the search for new antimicrobials from different sources, including deep oceans/seas. In this study, 675 extracts obtained from 225 cyanobacteria and microalgae species (11 phyla and 6 samples belonging to unknown group) were obtained from different culture collections: The Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC), the Coimbra Collection of Algae (ACOI) from Portugal, and the Roscoff Culture Collection (RCC) from France. The largest number of samples was made up of the microalgae phylum Chlorophyta (270) followed by Cyanobacteria (261). To obtain a large range of new bioactive compounds, a method involving three consecutive extractions (hexane, ethyl acetate, and methanol) was used. The antibiofilm activity of extracts was determined against seven different bacterial species and two Candida strains in terms of minimal biofilm inhibitory concentration (MBIC). The highest biofilm inhibition rates (%) were achieved against Candida albicans and Enterobacter cloacae. Charophyta, Chlorophyta, and Cyanobacteria were the most effective against all microorganisms. In particular, extracts of Cercozoa phylum presented the lowest MBIC50 and MBIC90 values for all the strains except C. albicans

The essentials of marine biotechnology.

Coastal countries have traditionally relied on the existing marine resources (e.g., fishing, food, transport, recreation, and tourism) as well as tried to support new economic endeavors (ocean energy, desalination for water supply, and seabed mining). Modern societies and lifestyle resulted in an increased demand for dietary diversity, better health and well-being, new biomedicines, natural cosmeceuticals, environmental conservation, and sustainable energy sources. These societal needs stimulated the interest of researchers on the diverse and underexplored marine environments as promising and sustainable sources of biomolecules and biomass, and they are addressed by the emerging field of marine (blue) biotechnology. Blue biotechnology provides opportunities for a wide range of initiatives of commercial interest for the pharmaceutical, biomedical, cosmetic, nutraceutical, food, feed, agricultural, and related industries. This article synthesizes the essence, opportunities, responsibilities, and challenges encountered in marine biotechnology and outlines the attainment and valorization of directly derived or bio-inspired products from marine organisms. First, the concept of bioeconomy is introduced. Then, the diversity of marine bioresources including an overview of the most prominent marine organisms and their potential for biotechnological uses are described. This is followed by introducing methodologies for exploration of these resources and the main use case scenarios in energy, food and feed, agronomy, bioremediation and climate change, cosmeceuticals, bio-inspired materials, healthcare, and well-being sectors. The key aspects in the fields of legislation and funding are provided, with the emphasis on the importance of communication and stakeholder engagement at all levels of biotechnology development. Finally, vital overarching concepts, such as the quadruple helix and Responsible Research and Innovation principle are highlighted as important to follow within the marine biotechnology field. The authors of this review are collaborating under the European Commission-funded Cooperation in Science and Technology (COST) Action Ocean4Biotech – European transdisciplinary networking platform for marine biotechnology and focus the study on the European state of affairs

Synthèse de peptides et de PNAs dirigés contre les ARN du VHC et du VIH-1 (activité antivirale et pénétration cellulaire)

Les antiviraux actuels, dirigés contre les enzymes virales du VHC et du VIH, conduisent à l émergence rapide de souches résistantes. Une approche intéressante pour contourner ce problème consiste à cibler des fragments d ARN non traduits. De façon générale, deux approches sont envisagées pour cibler des fragments d ARN : l inhibition par des petites molécules et l approche antisens. Dans le cadre de la recherche de petites molécules dirigées contre les deux boucles E des domaines IIb et IIId de l IRES du VHC, nous avons synthétisé 52 peptides et dérivés de peptides linéaires et cycliques contenant la séquence d acides aminés Lys-Lys-Pro-Lys. En parallèle, nous avons tenté d améliorer la pénétration cellulaire d oligonucléotides antisens de type PNA. Ainsi, nous avons synthétisé deux synthons contenant un groupement fluorescent et une cystéine liée au cation lipophile 4-thiobutyltriphénylphosphonium (TBTP) via un pont disulfure biolabile en milieu réducteur. Nous avons conjugué ces synthons à un PNA cyclique dirigé contre la boucle SL3 du VIH et étudié la pénétration cellulaire par microscopie de fluorescence et cytométrie de flux. Nous avons montré que la pénétration cellulaire de ces conjugués de PNA n a pas lieu par un processus d endocytose, sensible à la température ou dépendant de l ATP, mais par une translocation passive à travers la bicouche lipidique de la membrane cellulaire. Finalement, nous avons synthétisé un second type de vecteur constitué du TBTP lié, via un pont disulfure, au 2-mercaptoéthanol, qui, une fois conjugué aux PNAs par une liaison de type carbamate, est susceptible de délivrer ces derniers intacts dans le cytoplasme de la cellule (non liés à un groupement résiduel).Current antiviral drugs, directed against viral enzymes of HCV and HIV, lead to the fast emergence of resistant variants. An interesting approach to circumvent this problem consists in targeting untranslated RNA fragments. In a general way, two approaches are envisaged to target RNA fragments: the inhibition by small molecules and the antisens approach. We have synthesized 52 linear and cyclic peptides and peptide derivatives constituted by the amino-acids sequence Lys-Lys-Pro-Lys targeting the two E loops of the HCV RNA. In parallel, we have tried to improve the cellular uptake of antisens PNA. We have synthesized two cysteine synthon incorporating both a fluorescent group and a triphenylphosphonium derivative (TBTP) via an intracellular scissile disulphide bond. We have conjugated these synthons to a cyclic PNA-based compound and investigated the cellular uptake of these conjugates by fluorescence microscopy and flow cytometry. We have shown that the cellular uptake of these cyclic PNA conjugates is not driven by an endocytotic temperature-sensitive or ATP-dependent process but by a passive translocation through the lipid matrix of the cell membrane. Finally, we have synthesized a second vector constituted by TBTP linked, via a disulfide bond, to 2-mercaptoethanol, which, once conjugated to PNAs by a carbamate bond, could release an unaltered PNA in the cytoplasm of the cell.NICE-BU Sciences (060882101) / SudocSudocFranceF

Outstanding marine biotoxins: STX, TTX, and CTX

Countless marine species, including invertebrates, are able to produce, accumulate and use a variety of toxins for predation and defense. Many of those marine toxins arise from toxic microscopic algae that are accumulated through the marine food-chain and can contaminate seafood to cause food poisoning, including various neurological and gastrointestinal illnesses in humans. The most important toxic syndromes associated with marine toxin contamination are paralytic shellfish poisoning (PSP), diarrhetic shellfish poisoning (DSP), amnesic shellfish poisoning (ASP), neurotoxic shellfish poisoning (NSP), ciguatera fish poisoning (CFP), and the well-known pufferfish poisoning (PFP), with each related to marine toxins with specific chemical structures and biological properties. In this chapter, attention is focused on PSP, PFP, and CFP that are produced by the saxitoxins, tetrodotoxins and ciguatoxins, respectively