Atmospheric Precipitations, Hailstone and Rainwater, as a Novel Source of Streptomyces Producing Bioactive Natural Products

A cultivation-dependent approach revealed that highly diverse populations of Streptomyces were present in atmospheric precipitations from a hailstorm event sampled in February 2016 in the Cantabrian Sea coast, North of Spain. A total of 29 bioactive Streptomyces strains isolated from small samples of hailstone and rainwater, collected from this hailstorm event, were studied here. Taxonomic identification by 16S rRNA sequencing revealed more than 20 different Streptomyces species, with their closest homologs displaying mainly oceanic but also terrestrial origins. Backward trajectory analysis revealed that the air-mass sources of the hailstorm event, with North Western winds, were originated in the Arctic Ocean (West Greenland and North Iceland) and Canada (Labrador), depending on the altitude. After traveling across the North Atlantic Ocean during 4 days the air mass reached Europe and precipitated as hailstone and rain water at the sampling place in Spain. The finding of Streptomyces species able to survive and disperse through the atmosphere increases our knowledge of the biogeography of genus Streptomyces on Earth, and reinforces our previous dispersion model, suggesting a generalized feature for the genus which could have been essential in his evolution. This unique atmospheric-derived Streptomyces collection was screened for production of bioactive secondary metabolites. Analyses of isolates ethyl acetate extracts by LC-UV-MS and further database comparison revealed an extraordinary diversity of bioactive natural products. One hundred molecules were identified, mostly displaying contrasted antibiotic and antitumor/cytotoxic activities, but also antiparasitic, antiviral, anti-inflammatory, neuroprotector, and insecticide properties. More interestingly, 38 molecules not identified in natural products databases might represent new natural products. Our results revealed for the first time an extraordinary diversity of Streptomyces species in the atmosphere able to produce an extraordinary repertoire of bioactive molecules, thus providing a very promising source for the discovery of novel pharmaceutical natural products

Anthracimycin B, a Potent Antibiotic against Gram-Positive Bacteria Isolated from Cultures of the Deep-Sea Actinomycete <i>Streptomyces cyaneofuscatus</i> M-169

The potent antimicrobial extract of a culture of the marine derived actinomycete Streptomyces cyaneofuscatus M-169 was fractionated by reversed phase flash chromatography and preparative HPLC to yield the new Gram-positive antibiotic, anthracimycin B (1), together with its congener, anthracimycin (2). The structure of the new compound was established by analysis of its ESI-TOF MS and 1D and 2D NMR spectra, and comparison with data published for anthracimycin and anthracimycin BII-2619 (3). Notably, anthracimycin seemed to be the major and almost unique component of the extract detected by HPLC-UV-MS, making our S. cyanofuscatus strain an excellent candidate for further biosynthetic studies of this potent antibiotic

New 3-Hydroxyquinaldic Acid Derivatives from Cultures of the Marine Derived Actinomycete Streptomyces cyaneofuscatus M-157

Fractionation of the bioactive extract of a culture of the marine derived actinomycete Streptomyces cyaneofuscatus M-157 led to the isolation of the known 3-hydroxyquinaldic acid (4), its amide (5) and three new derivatives (1&ndash;3) containing different amino acid residues. The structures of the new molecules (1&ndash;3), including their absolute configuration, were determined by the analysis of their ESI-TOF MS and one-dimensional (1D) and two-dimensional (2D) NMR spectra and advanced Marfey&rsquo;s analysis of their hydrolyzation products. Compound 3 spontaneously dimerized in solution to give the disulfide derivative 6. Unfortunately, none of the new compounds isolated confirmed the antimicrobial activity found in the bacterial extract, perhaps indicating that such antibacterial activity might be due to presence in the extract at the trace level of larger bioactive 3-hydroxyquinaldic acid derivatives from which compounds 1&ndash;3 are biosynthetic precursors. Cytotoxicity tests confirmed the moderate and weak IC50 values of 15.6 and 51.5 &micro;M for compounds 5 and 1, respectively

Relationship between exclusive breastfeeding and brain-derived neurotrophic factor in children.

ObjectiveA positive relationship between breastfeeding and brain-derived neurotrophic factor (BDNF) in infants has been suggested due to the presence of BDNF in human milk. This study aimed to determine the relationship between exclusive breastfeeding and BDNF serum levels in Spanish schoolchildren.MethodsA cross-sectional analysis including 202 schoolchildren, aged eight to 11 years, from Cuenca, Spain, was conducted. Information on sociodemographic and anthropometric variables, sexual maturation, birth weight and exclusive breastfeeding ('no exclusive breastfeeding', and exclusive breastfeeding for ≤6 and >6 months), and BDNF serum levels using an ELISA method were obtained. Covariance analyses (ANCOVA) were conducted to examine the relationship between serological BDNF and exclusive breastfeeding after controlling for potential confounders.ResultsANCOVA models showed no significant differences in BDNF levels between children who were exclusively breastfed for more than six months versus those who were not (p > 0.05). No significant differences were observed by age group (eight to nine years versus 10 to 11 years; p > 0.05). Additionally, no clear negative trend in BDNF serum levels according to sexual maturation categories was found (p > 0.05).ConclusionThese findings suggest that exclusive breastfeeding does not have a significant positive association on BDNF from eight to 11 years, since children who were exclusively breastfed did not have significantly higher BDNF levels than those who were not exclusively breastfed. Likewise, BDNF levels were not found to be negatively affected by hormonal development. Future research should examine the influence of exclusive breastfeeding on BDNF over the different developmental stages

Image1_Atmospheric Precipitations, Hailstone and Rainwater, as a Novel Source of Streptomyces Producing Bioactive Natural Products.PDF

<p>A cultivation-dependent approach revealed that highly diverse populations of Streptomyces were present in atmospheric precipitations from a hailstorm event sampled in February 2016 in the Cantabrian Sea coast, North of Spain. A total of 29 bioactive Streptomyces strains isolated from small samples of hailstone and rainwater, collected from this hailstorm event, were studied here. Taxonomic identification by 16S rRNA sequencing revealed more than 20 different Streptomyces species, with their closest homologs displaying mainly oceanic but also terrestrial origins. Backward trajectory analysis revealed that the air-mass sources of the hailstorm event, with North Western winds, were originated in the Arctic Ocean (West Greenland and North Iceland) and Canada (Labrador), depending on the altitude. After traveling across the North Atlantic Ocean during 4 days the air mass reached Europe and precipitated as hailstone and rain water at the sampling place in Spain. The finding of Streptomyces species able to survive and disperse through the atmosphere increases our knowledge of the biogeography of genus Streptomyces on Earth, and reinforces our previous dispersion model, suggesting a generalized feature for the genus which could have been essential in his evolution. This unique atmospheric-derived Streptomyces collection was screened for production of bioactive secondary metabolites. Analyses of isolates ethyl acetate extracts by LC-UV-MS and further database comparison revealed an extraordinary diversity of bioactive natural products. One hundred molecules were identified, mostly displaying contrasted antibiotic and antitumor/cytotoxic activities, but also antiparasitic, antiviral, anti-inflammatory, neuroprotector, and insecticide properties. More interestingly, 38 molecules not identified in natural products databases might represent new natural products. Our results revealed for the first time an extraordinary diversity of Streptomyces species in the atmosphere able to produce an extraordinary repertoire of bioactive molecules, thus providing a very promising source for the discovery of novel pharmaceutical natural products.</p

Branimycins B and C, Antibiotics Produced by the Abyssal Actinobacterium Pseudonocardia carboxydivorans M-227.

Two new antibiotics, branimycins B (2) and C (3), were produced by fermentation of the abyssal actinobacterium Pseudonocardia carboxydivorans M-227, isolated from deep seawater of the Avilés submarine Canyon. Their structures were elucidated by HRMS and NMR analyses. These compounds exhibit antibacterial activities against a panel of Gram-positive bacteria, including Corynebacterium urealyticum, Clostridium perfringens, and Micrococcus luteus, and against the Gram-negative bacterium Neisseria meningitidis. Additionally, branimycin B displayed moderate antibacterial activity against other Gram-negative bacteria such as Bacteroides fragilis, Haemophilus influenzae, and Escherichia coli, and branimycin C against the Gram-positive Enterococcus faecalis and methicillin-sensitive and methicillin-resistant Staphylococcus aureus

Desertomycin G, a New Antibiotic with Activity against <i>Mycobacterium tuberculosis</i> and Human Breast Tumor Cell Lines Produced by <i>Streptomyces althioticus</i> MSM3, Isolated from the Cantabrian Sea Intertidal Macroalgae <i>Ulva</i> sp.

The isolation and structural elucidation of a structurally new desertomycin, designated as desertomycin G (1), with strong antibiotic activity against several clinically relevant antibiotic resistant pathogens are described herein. This new natural product was obtained from cultures of the marine actinomycete Streptomyces althioticus MSM3, isolated from samples of the intertidal seaweed Ulva sp. collected in the Cantabrian Sea (Northeast Atlantic Ocean). Particularly interesting is its strong antibiotic activity against Mycobacterium tuberculosis clinical isolates, resistant to antibiotics in clinical use. To the best of our knowledge, this is the first report on a member of the desertomycin family displaying such activity. Additionally, desertomycin G shows strong antibiotic activities against other relevant Gram-positive clinical pathogens such as Corynebacterium urealyticum, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecium, Enterococcus faecalis, and Clostridium perfringens. Desertomycin G also displays moderate antibiotic activity against relevant Gram-negative clinical pathogens such as Bacteroides fragilis, Haemophilus influenzae and Neisseria meningitidis. In addition, the compound affects viability of tumor cell lines, such as human breast adenocarcinoma (MCF-7) and colon carcinoma (DLD-1), but not normal mammary fibroblasts