Marine Sponge-associated Fungi Research Articles

Identification of a marine-derived sesquiterpenoid, Compound-8, that inhibits tumour necrosis factor-induced cell death by blocking complex II assembly.

Tumour necrosis factor (TNF) is a pleiotropic inflammatory cytokine that not only directly induces inflammatory gene expression but also triggers apoptotic and necroptotic cell death, which leads to tissue damage and indirectly exacerbates inflammation. Thus, identification of inhibitors for TNF-induced cell death has broad therapeutic relevance for TNF-related inflammatory diseases. In the present study, we isolated and identified a marine fungus-derived sesquiterpenoid, 9α,14-dihydroxy-6β-p-nitrobenzoylcinnamolide (named as Cpd-8), that inhibits TNF receptor superfamily-induced cell death by preventing the formation of cytosolic death complex II. Marine sponge-associated fungi were cultured and the secondary metabolites were extracted to yield pure compounds. Cell viability was measured by ATP-Glo cell viability assay. The effects of Cpd-8 on TNF signalling pathway were investigated by western blotting, immunoprecipitation, and immunofluorescence assays. A mouse model of acute liver injury (ALI) was employed to explore the protection effect of Cpd-8, in vivo. Cpd-8 selectively inhibits TNF receptor superfamily-induced apoptosis and necroptosis. Cpd-8 prevents the formation of cytosolic death complex II and subsequent RIPK1-RIPK3 necrosome, while it has no effect on TNF receptor I (TNFR1) internalization and the formation of complex I in TNF signalling pathway. In vivo, Cpd-8 protects mice against TNF-α/D-GalN-induced ALI. A marine fungus-derived sesquiterpenoid, Cpd-8, inhibits TNF receptor superfamily-induced cell death, both in vitro and in vivo. This study not only provides a useful research tool to investigate the regulatory mechanisms of TNF-induced cell death but also identifies a promising lead compound for future drug development.

Discovery of Cymopolyphenols A-F From a Marine Mesophotic Zone Aaptos Sponge-Associated Fungus Cymostachys sp. NBUF082.

Mesophotic coral ecosystems (MCEs) have complex but understudied biodiversity, especially for natural products discovery. Untargeted metabolomics research on 80 extracts prepared from marine sponge-associated fungi, half from shallow reefs (<30 m) and half from MCEs (30–150 m), facilitated prioritization for further study a Cymostachys fungus from a 103 m deep Aaptos sponge. LC-MS target-directed isolation yielded a series of new compounds, cymopolyphenols A−F (1–6), and two known phenylspirodrimanes, F1839-I (7) and stachybotrylactone (8). This is the first report of natural products from the recently described genus, Cymostachys. Compounds 1–6 and 8 contain a dihydroisobenzofuran moiety, and 4–6 are low-order polymers of 1 with novel scaffolds. The structures of the compounds were established by spectroscopic and spectrometric data interpretation, with further support from X-ray crystallography studies of 3 and 4. Compound 3 undergoes facile racemization in solution and was found to crystalize as a racemic mixture. Compound 5 was also obtained in racemic form, and after chiral chromatography, both separated enantiomers racemized in solution by a presumed keto-enol tautomerization. Compounds 1 and 3–6 were found to be weakly antimicrobial (MIC 16–64 μg/ml) in vitro against several Gram-positive and Gram-negative human or aquatic pathogens, compound 5 was shown to chelate iron in vitro at 10 μM, and 8 activated plant disease resistance in vivo in a transgenic model organism.

Marine Sponge-Associated Fungi as Potential Novel Bioactive Natural Product Sources for Drug Discovery: A Review

Marine sponge-associated fungi are promising sources of structurally interesting and bioactive secondary metabolites. Great plenty of natural products have been discovered from spongeassociated fungi in recent years. Here reviewed are 571 new compounds isolated from marine fungi associated with sponges in 2010-2018. These molecules comprised eight different structural classes, including alkaloids, polyketides, terpenoids, meroterpenoids, etc. Moreover, most of these compounds demonstrated profoundly biological activities, such as antimicrobial, antiviral, cytotoxic, etc. This review systematically summarized the structural diversity, biological function, and future potential of these novel bioactive natural products for drug discovery.

Design and Synthesis of Novel Anti-Proliferative Emodin Derivatives and Studies on their Cell Cycle Arrest, Apoptosis Pathway and Migration.

Emodin is a cell arrest and apoptosis-inducing compound that is widely distributed in different plants (rhubarb, aloe), lichens and terrestrial fungi, and also isolated from marine-derived fungi and marine sponge-associated fungi. In this study, we designed and synthesized a novel series of emodin derivatives by binding emodin to an amino acid using linkers of varying lengths and composition, and evaluated their anti-proliferative activities using HepG2 cells (human hepatic carcinoma), MCF-7 cells (human breast cancer) and human normal liver L02 cells. Most of these derivatives showed moderate to potent anti-proliferative activities. Notably, compound 7a exhibited potent anti-proliferative activity against HepG2 cells with the half maximal inhibitory concentration (IC50) value of 4.95 µM, which was enhanced 8.8-fold compared to the parent compound emodin (IC50 = 43.87 µM), and it also exhibited better selective anti-proliferative activity and specificity than emodin. Moreover, further experiments demonstrated that compound 7a displayed a significant efficacy of inducing apoptosis through mitochondrial pathway via release of cytochrome c from mitochondria and subsequent activation of caspase-9 and caspase-3, inducing cell arrest at G0/G1 phase, as well as suppression of cell migration of tumor cells. The preliminary results suggested that compound 7a could be a promising lead compound for the discovery of novel anti-tumor drugs and has the potential for further investigations as an anti-cancer drug.

Antimicrobial evaluation of the crude extract of symbiotic fungi from marine sponge Reniera japonica

&lt;p&gt;Marine sponge-derived microbes are one of the rich sources of bioactive natural products with a broad spectrum of bioactivities. The present work focuses on the isolation and antimicrobial screening of the marine sponge-associated fungi from Reniera japonica MNP-2016. The results indicated that five fungi (L1-2, L2-1, L4, L8-1 and L14) were successfully isolated. Bioassay tests showed that only strain L14 had strong inhibitory effect on the pathogens, Staphyloccocus aureus, Escherichia coli and Candida albicans. 18S rDNA sequence analysis indicated that strain L14 was ascribed to Aspergillus genus. To the best of our knowledge, this work was the first report on the isolation and antimicrobial evaluation of fungi from R. japonica.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Video Clip of Methodology&lt;/strong&gt;:&lt;/p&gt;&lt;p&gt;1 min 13 sec: &lt;a href="https://www.youtube.com/v/RSA2icw3emg"&gt;Full Screen&lt;/a&gt; &lt;a href="https://www.youtube.com/watch?v=RSA2icw3emg"&gt;Alternate&lt;/a&gt;&lt;/p&gt;

Evaluation of Antimicrobial Activity and Identification of Yellow Pigmented Marine Sponge-Associated Fungi from Teluk Awur, Jepara, Central Java

Marine sponge associated fungi are known as potential source of metabolites with various biological activities. Natural pigment is one of metabolite which produced by microorgisms. Several researches reported the antimicrobial activity from natural pigment. Unfortunatelly there are lack of information about marine fungi natural pigment and its producer. The aims of this research were to identify yellow pigmented Indonesian marine sponge-associated fungi, to extract the pigment, and to study the antimicrobial activity of the pigment against clinical MDR bacteria and clinical pathogenic fungi. Sponge associated-fungus isolate MT23 was successfully identified as Trichoderma parareesei. The fungal pigment could be extracted only in methanol with yield 6,22±0,29%. The pigment could inhibitted S. typhi and E. coli MDR strains. The biggest antibacterial activity was shown by concentration 1000µg/mL against S. typhi with inhibition zone was 4.03±0.06 mm.

Isolation, Identification And Screening Antibacterial Activity from Marine Sponge-Associated Fungi Against Multidrug-Resistant (MDR) Escherichia coli

Irrational used of antibiotic in several decades ago causing resistant in bacteria and decreasing the cure rate of infectious diseases. Multidrug-resistant (MDR) Escherichia coli is known to cause various of infectious diseases such as urinary tract infection, nosocomial bloodstream infection, meningitis, bacteraemia, and gastrointestinal disease. Marine sponge-associated fungi have potential as source of new compound to combat MDR E. coli. The aims of this research were to isolate marine sponge-assosiated fungi, to screen potential fungi against MDR E. coli, to identify the potential fungi and its host sponge. There were 29 marine sponge-associated fungi successfully isolated from 9 sponges. Among 29 sponge-associated fungi screened, there were 7 isolates showed antibacterial activity against MDR E. coli. The best inhibition zone produced by MPS 14.1/MT 02 and MPS 14.3/MT 04 from sponge PP.SP.16.14. According to fungi identification result fungus MPS 14.1/MT 02 was identified as Trichoderma asperellum while MPS 14.3/MT 04 was identified as Trichoderma reesei. Sponge identification leaded the PP.SP.16.14 as Cinachyrella sp.

Screening of Antibacterial MDR derived from Sponge Associated Fungus of Riung Water, Nusa Tenggara Timur

Marine sponge-associated fungi are the sources of bioactive compounds with various pharmacologicals potency . This study aim ed to isolate the sponge-associated fungi as the producer of the MDR anti - bacteria l compounds. The associated fungi were isolated from the sponges collected from Riung water, Nusa Tenggara Timur . Five of the best isolates were cultured on MEA to obtain the methanolic extract for further studies . The antagonistic test was conducted using overlay method towards the MDR Staphylococcus aureus and Escherichia coli. A total of 33 fungi were isolated from 19 sponge specimens. The antagonistic test showed that 19 isolates were active against both S. aureus and E. coli , and 13 of them were merely active against one of the bacteria. However, only five isolates have strong activity against one or both of the bacteria. The KN-15-3 ha d the strongest activity against S. aureus ( 18.75±0.777 mm) an d E. coli ( 15.10±0.141 mm) at the concentration of 400 μg.dis c -1 so it can be developed further as a source of drug candicate . K eywords : F ungi symbion t, Spon ges , MDR A nti bacteria l , Staphylococcus aureus, Escherichia coli.

Purification, Chemical Characterization, and Bioactivity of an Extracellular Polysaccharide Produced by the Marine Sponge Endogenous Fungus Alternaria sp. SP-32.

Marine sponges are ancient and simple multicellular filter-feeding invertebrates attached to solid substrates in benthic habitats and host a variety of fungi both inside and on their surface because of its unique ingestion and digest system. Investigation on marine sponge-associated fungi mainly focused on the small molecular metabolites, yet little attention had been paid to the extracellular polysaccharides. In this study, a homogeneous extracellular polysaccharide AS2-1 was obtained from the fermented broth of the marine sponge endogenous fungus Alternaria sp. SP-32 using ethanol precipitation, anion-exchange, and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that AS2-1 was composed of mannose, glucose, and galactose with a molar ratio of 1.00:0.67:0.35, and its molecular weight was 27.4kDa. AS2-1 consists of a mannan core and a galactoglucan chain. The mannan core is composed of (1→6)-α-Manp substituted at C-2 by (1→2)-α-Manp with different degrees of polymerization. The galactoglucan chain consists of (1→6)-α-Glcp residues with (1→6)-β-Galf residues attached to the last glucopyranose residue at C-6. (1→6)-β-Galf residues have additional branches at C-2 consisting of disaccharide units of (1→2)-β-Galf and (1→2)-α-Glcp residues. The glucopyranose residue of the galactoglucan chain is linked to the mannan core. AS2-1 possessed a high antioxidant activity as evaluated by scavenging of 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radicals in vitro. AS2-1 was also evaluated for cytotoxic activity on Hela, HL-60, and K562 cell lines by the MTT and SRB methods. The investigation demonstrated that AS2-1 was a novel extracellular polysaccharide with different characterization from extracellular polysaccharides produced by other marine microorganisms.

Cytotoxic Nitrobenzoyloxy-substituted Sesquiterpenes from Spongederived Endozoic Fungus Aspergillus insulicola MD10-2.

The emergence of drug resistance and spread of new infectious diseases necessitated the development of novel antibiotics. Marine sponge-associated fungi represent a reservoir of novel molecules with diverse biological potentials. In this study, we isolated five nitrobenzoyloxy-substituted sesquiterpenes 1-5 from the culture mycelia of an endozoic fungus Aspergillus insulicola MD10-2, obtained from the South China Sea sponge Cinachyrella australiensis. Compound 2 showed cytotoxicity against human lung cancer cell line H-460 with an IC50 value of 6.9 µM. Cytotoxicity of the acetylated derivatives (2a and 2b) of compound 2 decreased markedly, suggesting that the hydroxyl group contributed to the cytotoxic activity. Compound 5 was inactive against H-460, which implied the double bond at C-7 had an effect on cytotoxic activity as well.

Phylogenetic diversity of culturable fungi associated with the Hawaiian Sponges Suberites zeteki and Gelliodes fibrosa

Sponges are well documented to harbor large amounts of microbes. Both culture-dependent and molecular approaches have revealed remarkable bacterial diversity in marine sponges. Fungi are commonly isolated from marine sponges, yet no reports on phylogenetic diversity of sponge-inhabiting fungi exist. In this report, we investigated the phylogenetic diversity of culturable fungi from the Hawaiian alien marine sponges Suberites zeteki and Gelliodes fibrosa. A total of 44 independent isolates were recovered from these two sponge species, representing 7 orders and 22 genera of Ascomycota. The majority (58%) of fungal isolates from S. zeteki resided in the Pleosporales group, while the predominant isolates (52%) from G. fibrosa were members of the Hypocreales group. Though differing in fungal species composition and structure, culturable communities of these two sponges displayed similar phylogenetic diversity. At the genus level, only two genera Penicillium and Trichoderma in the Eurotiales and Hypocreales orders, respectively, were present in both sponge species. The other genera of the fungal isolates were associated with either S. zeteki or G. fibrosa. Some of these fungal genera had been isolated from sponges collected in other marine habitats, but more than half of these genera were identified for the first time in these two marine sponges. Overall, the diversity of culturable fungal communities from these two sponge species is much higher than that observed in studies of marine sponges from other areas. This is the first report of phylogenetic diversity of marine sponge-associated fungi and adds one more dimension to our current understanding of the phylogenetic diversity of sponge-symbiotic microbes.