Biotechnological Potential of Bacteria Isolated from the Sea Cucumber Holothuria leucospilota and Stichopus vastus from Lampung, Indonesia

In order to minimize re-discovery of already known anti-infective compounds, we focused our screening approach on understudied, almost untapped marine environments including marine invertebrates and their associated bacteria. Therefore, two sea cucumber species, Holothuria leucospilota and Stichopus vastus, were collected from Lampung (Indonesia), and 127 bacterial strains were identified by partial 16S rRNA-gene sequencing analysis and compared with the NCBI database. In addition, the overall bacterial diversity from tissue samples of the sea cucumbers H. leucospilota and S. vastus was analyzed using the cultivation-independent Illumina MiSEQ analysis. Selected bacterial isolates were grown to high densities and the extracted biomass was tested against a selection of bacteria and fungi as well as the hepatitis C virus (HCV). Identification of putative bioactive bacterial-derived compounds were performed by analyzing the accurate mass of the precursor/parent ions (MS1) as well as product/daughter ions (MS2) using high resolution mass spectrometry (HRMS) analysis of all active fractions. With this attempt we were able to identify 23 putatively known and two previously unidentified precursor ions. Moreover, through 16S rRNA-gene sequencing we were able to identify putatively novel bacterial species from the phyla Actinobacteria, Proteobacteria and also Firmicutes. Our findings suggest that sea cucumbers like H. leucospilota and S. vastus are promising sources for the isolation of novel bacterial species that produce compounds with potentially high biotechnological potential

Brain MR patterns in inherited disorders of monoamine neurotransmitters: An analysis of 70 patients

Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analysed brain MRIs in order to characterize and better understand neuroimaging changes and to re-evaluate the diagnostic role of brain MRI in iMNDs

Symbionts as Major Modulators of Insect Health: Lactic Acid Bacteria and Honeybees

Lactic acid bacteria (LAB) are well recognized beneficial host-associated members of the microbiota of humans and animals. Yet LAB-associations of invertebrates have been poorly characterized and their functions remain obscure. Here we show that honeybees possess an abundant, diverse and ancient LAB microbiota in their honey crop with beneficial effects for bee health, defending them against microbial threats. Our studies of LAB in all extant honeybee species plus related apid bees reveal one of the largest collections of novel species from the genera Lactobacillus and Bifidobacterium ever discovered within a single insect and suggest a long (>80 mya) history of association. Bee associated microbiotas highlight Lactobacillus kunkeei as the dominant LAB member. Those showing potent antimicrobial properties are acquired by callow honey bee workers from nestmates and maintained within the crop in biofilms, though beekeeping management practices can negatively impact this microbiota. Prophylactic practices that enhance LAB, or supplementary feeding of LAB, may serve in integrated approaches to sustainable pollinator service provision. We anticipate this microbiota will become central to studies on honeybee health, including colony collapse disorder, and act as an exemplar case of insect-microbe symbiosis

Diversity of Myxobacteria—We Only See the Tip of the Iceberg

The discovery of new antibiotics is mandatory with regard to the increasing number of resistant pathogens. One approach is the search for new antibiotic producers in nature. Among actinomycetes, Bacillus species, and fungi, myxobacteria have been a rich source for bioactive secondary metabolites for decades. To date, about 600 substances could be described, many of them with antibacterial, antifungal, or cytostatic activity. But, recent cultivation-independent studies on marine, terrestrial, or uncommon habitats unequivocally demonstrate that the number of uncultured myxobacteria is much higher than would be expected from the number of cultivated strains. Although several highly promising myxobacterial taxa have been identified recently, this so-called Great Plate Count Anomaly must be overcome to get broader access to new secondary metabolite producers. In the last years it turned out that especially new species, genera, and families of myxobacteria are promising sources for new bioactive metabolites. Therefore, the cultivation of the hitherto uncultivable ones is our biggest challenge

Volatiles from the tropical ascomycete (Hypoxylaceae, Xylariales).

The volatiles from the fungus Daldinia clavata were collected by use of a closed-loop stripping apparatus and analysed by GC-MS. A few compounds were readily identified by comparison of measured to library mass spectra and of retention indices to published data, while for other compounds a synthesis of references was required. For one of the main compounds, 5-hydroxy-4,6-dimethyloctan-3-one, the relative and absolute configuration was determined by synthesis of all eight stereoisomers and gas chromatographic analysis using a homochiral stationary phase. Another identified new natural product is 6-nonyl-2H-pyran-2-one. The antimicrobial and cytotoxic effects of the synthetic volatiles are also reported

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

The volatiles from the fungus Daldinia clavata were collected by use of a closed-loop stripping apparatus and analysed by GC–MS. A few compounds were readily identified by comparison of measured to library mass spectra and of retention indices to published data, while for other compounds a synthesis of references was required. For one of the main compounds, 5-hydroxy-4,6-dimethyloctan-3-one, the relative and absolute configuration was determined by synthesis of all eight stereoisomers and gas chromatographic analysis using a homochiral stationary phase. Another identified new natural product is 6-nonyl-2H-pyran-2-one. The antimicrobial and cytotoxic effects of the synthetic volatiles are also reported

Anti-Infective and Antiviral Activity of Valinomycin and Its Analogues from a Sea Cucumber-Associated Bacterium, Streptomyces sp. SV 21

The manuscript investigated the isolation, characterization and anti-infective potential of valinomycin (3), streptodepsipeptide P11A (2), streptodepsipeptide P11B (1), and one novel valinomycin analogue, streptodepsipeptide SV21 (4), which were all produced by the Gram-positive strain Streptomycescavourensis SV 21. Although the exact molecular weight and major molecular fragments were recently reported for compound 4, its structure elucidation was not based on compound isolation and spectroscopic techniques. We successfully isolated and elucidated the structure based on the MS2 fragmentation pathways as well as 1H and 13C NMR spectra and found that the previously reported structure of compound 4 differs from our analysis. Our findings showed the importance of isolation and structure elucidation of bacterial compounds in the era of fast omics technologies. The here performed anti-infective assays showed moderate to potent activity against fungi, multi drug resistant (MDR) bacteria and infectivity of the Hepatitis C Virus (HCV). While compounds 2, 3 and 4 revealed potent antiviral activity, the observed minor cytotoxicity needs further investigation. Furthermore, the here performed anti-infective assays disclosed that the symmetry of the valinomycin molecule is most important for its bioactivity, a fact that has not been reported so far

Six Heterocyclic Metabolites from the Myxobacterium Labilithrix luteola

Two new secondary metabolites, labindole A [2-methyl-3-(2-nitroethyl)-3H-indole] (1) and labindole B [2-methyl-3-(2-nitrovinyl)-3H-indole] (2), were isolated from the myxobacterium Labilithrix luteola (DSM 27648T). Additionally, four metabolites 3, 4, 5 and 6 already known from other sources were obtained. Their structures were elucidated from high resolution electrospray ionisation mass spectrometry (HRESIMS) and 1D and 2D nuclear magnetic resonance (NMR) spectroscopy data and their relative configuration was assigned based on nuclear Overhauser effect (NOE) and vicinal 1H-NMR coupling data. The compounds where tested for biological activities; labindoles A (1) and B (2) exhibited significant activity against Hepatitis C Virus, 9H-carbazole (3), 3-chloro-9H-carbazole (4) and 4-hydroxymethyl-quinoline (5) showed antifungal activities. Moreover, compound 3 had weak to moderate antibacterial activities, while labindoles A (1) and B (2) were devoid of significant antifungal and antibacterial effects

Indothiazinone, an Indolyl Thiazolyl Ketone from a Novel Myxobacterium Belonging to the Sorangiineae

Indothiazinone (<b>1</b>), an indolyl thiazolyl ketone, was discovered in cultures of novel myxobacterial strain 706, recently isolated from compost in Germany. Molecular phylogenetic studies based on 16S rRNA gene sequences revealed strain 706 to be a representative of a new family of the Sorangiineae. A screening of the culture broth for antimicrobial metabolites followed by isolation and characterization of these compounds revealed six indole derivatives and a 1,4-naphthoquinone derivative. The structures were determined to be indothiazinone (<b>1</b>; 1<i>H</i>-indol-3-yl­(1,3-thiazol-2-yl)­methanone) and three 3-methylbuta-1,3-dien-1-yl-substituted indoles, indolyl ethanol <b>2</b> and the <i>E</i>- and <i>Z</i>-isomers of indolyl ethylidenehydroxylamine <b>4</b> and <b>5</b> by MS and NMR spectroscopic analyses. In the indolyl ethanol derivative <b>3</b> the unsaturated methylene group of the butadienyl residue was replaced by an oxygen atom to give the keto group of the butanone side chain. Further 1<i>H</i>-indol-3-ylacetonitrile (<b>6</b>) was identified, which was already known as a myxobacterial metabolite. 2-Hydroxyethyl-3-methyl-1,4-naphthoquinone (<b>7</b>) was recognized during dereplication as an antibiotic previously isolated from <i>Actinoplanes capillaceus</i>. Whereas <b>1</b>, <b>4</b>, <b>5</b>, and <b>7</b> showed weak activity against yeasts and filamentous fungi, isomers <b>4</b> and <b>5</b> were weakly active against Gram-positive bacteria and mouse fibroblasts. Compound <b>6</b> is volatile, and <b>2</b> and <b>3</b> showed no activity in a number of assays