95 research outputs found
Evaluation of Pyridoacridine Alkaloids in a Zebrafish Phenotypic Assay
Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1), 3-hydroxy-deoxyamphimedine (2), debromopetrosamine (3), and three known compounds, amphimedine (4), neoamphimedine (5) and deoxyamphimedine (6), have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1â6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4) was the only compound that caused a phenotype in zebrafish embryos at 30 ÎŒM. No phenotype other than death was observed for compounds 1â3, 5, 6
Burkholderia from fungus gardens of fungus-growing ants produce antifungals that inhibit the specialized parasite Escovopsis.
Within animal-associated microbiomes, the functional roles of specific microbial taxa are often uncharacterized. Here, we use the fungus-growing ant system, a model for microbial symbiosis, to determine the potential defensive roles of key bacterial taxa present in the antsâ fungus gardens. Fungus gardens serve as an external digestive system for the ants, with mutualistic fungi in the genus Leucoagaricus converting the plant substrate into energy for the ants. The fungus garden is host to specialized parasitic fungi in the genus Escovopsis. Here, we examine the potential role of Burkholderia spp. that occur within ant fungus gardens in inhibiting Escovopsis. We isolated members of the bacterial genera Burkholderia and Paraburkholderia from 50% of the 52 colonies sampled, indicating that members of the family Burkholderiaceae are common inhabitants in the fungus gardens of a diverse range of fungus-growing ant genera. Using antimicrobial inhibition bioassays, we found that 28 out of 32 isolates inhibited at least one Escovopsis strain with a zone of inhibition greater than 1cm. Genomic assessment of fungus garden-associated Burkholderiaceae indicated that isolates with strong inhibition all belonged to the genus Burkholderia and contained biosynthetic gene clusters that encoded the production of two antifungals: burkholdine1213 and pyrrolnitrin. Organic extracts of cultured isolates confirmed that these compounds are responsible for antifungal activities that inhibit Escovopsis but, at equivalent concentrations, not Leucoagaricus spp. Overall, these new findings, combined with previous evidence, suggest that members of the fungus garden microbiome play an important role in maintaining the health and function of fungus-growing ant colonies.National Institutes of Health/[U19 TW009872]/NIH/Estados UnidosNational Institutes of Health/[U19 AI142720]/NIH/Estados UnidosNational Institutes of Health/[T32 AI055397]/NIH/Estados UnidosNational Science Foundation/[DEB-1927155]/NSF/Estados UnidosSĂŁo Paulo Research Foundation/[2013/50954-0]/FAPESP/BrasilUCR::VicerrectorĂa de InvestigaciĂłn::Unidades de InvestigaciĂłn::Ciencias BĂĄsicas::Centro de InvestigaciĂłn en Estructuras MicroscĂłpicas (CIEMIC)UCR::VicerrectorĂa de InvestigaciĂłn::Unidades de InvestigaciĂłn::Ciencias BĂĄsicas::Centro de InvestigaciĂłn en BiologĂa Celular y Molecular (CIBCM)UCR::VicerrectorĂa de Docencia::Salud::Facultad de Medicina::Escuela de Medicin
New Tetromycin Derivatives with Anti-Trypanosomal and Protease Inhibitory Activities â
Four new tetromycin derivatives, tetromycins 1â4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001T cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV Mpro, and PLpro. The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with Ki values in the low micromolar range
Anti-Parasitic Compounds from Streptomyces sp. Strains Isolated from Mediterranean Sponges
Actinomycetes are prolific producers of pharmacologically important compounds accounting for about 70% of the naturally derived antibiotics that are currently in clinical use. In this study, we report on the isolation of Streptomyces sp. strains from Mediterranean sponges, on their secondary metabolite production and on their screening for anti-infective activities. Bioassay-guided isolation and purification yielded three previously known compounds namely, cyclic depsipeptide valinomycin, indolocarbazole alkaloid staurosporine and butenolide. This is the first report of the isolation of valinomycin from a marine source. These compounds exhibited novel anti-parasitic activities specifically against Leishmania major (valinomycin IC50 < 0.11 ÎŒM; staurosporine IC50 5.30 ÎŒM) and Trypanosoma brucei brucei (valinomycin IC50 0.0032 ÎŒM; staurosporine IC50 0.022 ÎŒM; butenolide IC50 31.77 ÎŒM). These results underscore the potential of marine actinomycetes to produce bioactive compounds as well as the re-evaluation of previously known compounds for novel anti-infective activities
Microtermolides A and B from Termite-Associated Streptomyces sp. and Structural Revision of Vinylamycin
Microtermolides A (1) and B (2) were isolated from a Streptomyces sp. strain associated with fungus-growing termites. The structures of 1 and 2 were determined by 1D- and 2D-NMR spectroscopy and high-resolution mass spectrometry. Structural elucidation of 1 led to the re-examination of the structure originally proposed for vinylamycin (3). Based on a comparison of predicted and experimental H and C NMR chemical shifts, we propose that vinylamycinâs structure be revised from 3 to 4
A community resource for paired genomic and metabolomic data mining
Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding identification of natural product biosynthetic origins and metabolite structures.Peer reviewe
- âŠ