RESUMEN
The "wooden-steps" hypothesis [Distel DL, et al. (2000) Nature 403:725-726] proposed that large chemosynthetic mussels found at deep-sea hydrothermal vents descend from much smaller species associated with sunken wood and other organic deposits, and that the endosymbionts of these progenitors made use of hydrogen sulfide from biogenic sources (e.g., decaying wood) rather than from vent fluids. Here, we show that wood has served not only as a stepping stone between habitats but also as a bridge between heterotrophic and chemoautotrophic symbiosis for the giant mud-boring bivalve Kuphus polythalamia This rare and enigmatic species, which achieves the greatest length of any extant bivalve, is the only described member of the wood-boring bivalve family Teredinidae (shipworms) that burrows in marine sediments rather than wood. We show that K. polythalamia harbors sulfur-oxidizing chemoautotrophic (thioautotrophic) bacteria instead of the cellulolytic symbionts that allow other shipworm species to consume wood as food. The characteristics of its symbionts, its phylogenetic position within Teredinidae, the reduction of its digestive system by comparison with other family members, and the loss of morphological features associated with wood digestion indicate that K. polythalamia is a chemoautotrophic bivalve descended from wood-feeding (xylotrophic) ancestors. This is an example in which a chemoautotrophic endosymbiosis arose by displacement of an ancestral heterotrophic symbiosis and a report of pure culture of a thioautotrophic endosymbiont.
Asunto(s)
Bacterias/metabolismo , Bivalvos/microbiología , Crecimiento Quimioautotrófico/fisiología , Simbiosis/fisiología , Madera/metabolismo , Animales , Madera/microbiologíaRESUMEN
New compounds nobilamides A-H and related known compounds A-3302-A and A-3302-B were isolated based upon their suppression of capsaicin-induced calcium uptake in a mouse dorsal root ganglion primary cell culture assay. Two of these compounds, nobilamide B and A-3302-A, were shown to be long-acting antagonists of mouse and human TRPV1 channels, abolishing activity for >1 h after removal of drug presumably via a covalent attachment. Other derivatives also inhibited the TRPV1 channel, albeit with low potency, affording a structure-activity profile to support the proposed mechanism of action. While the activities were modest, we propose a new mechanism of action and a new site of binding for these inhibitors that may spur development of related analogues for treatment of pain.
Asunto(s)
Depsipéptidos/síntesis química , Depsipéptidos/farmacología , Ganglios Espinales/efectos de los fármacos , Oligopéptidos/síntesis química , Oligopéptidos/farmacología , Streptomyces/química , Canales Catiónicos TRPV/antagonistas & inhibidores , Animales , Calcio/metabolismo , Capsaicina/antagonistas & inhibidores , Células Cultivadas , Depsipéptidos/química , Depsipéptidos/aislamiento & purificación , Ganglios Espinales/citología , Ganglios Espinales/metabolismo , Gastrópodos/microbiología , Células HEK293 , Humanos , Ratones , Estructura Molecular , Oligopéptidos/química , Oligopéptidos/aislamiento & purificación , Unión Proteica , Relación Estructura-Actividad , Factores de TiempoRESUMEN
The cone snail Conus pulicarius from the Philippines provides a specific habitat for actinomycetes and other bacteria. A phenotypic screen using primary cultures of mouse dorsal root ganglion neurons revealed that one C. pulicarius associate, Streptomyces sp. CP32, produces a series of natural products that enhance or diminish whole-cell Ca(2+) flux. These compounds include known thiazoline compounds and a series of new derivatives, pulicatins A-E (6-10). Individual compounds were shown to bind to a series of human receptors, with selective binding to the human serotonin 5-HT(2B) receptor. Here, we report the structure elucidation of the new compounds and results of the neurological assays.
Asunto(s)
Caracol Conus/microbiología , Tiazolidinas/aislamiento & purificación , Tiazolidinas/farmacología , Actinobacteria/crecimiento & desarrollo , Animales , Calcio/metabolismo , Humanos , Ratones , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Filipinas , Células del Asta Posterior/efectos de los fármacos , Células del Asta Posterior/metabolismo , Receptor de Serotonina 5-HT2B/metabolismo , Serotonina/metabolismo , Streptomyces/química , Streptomyces/crecimiento & desarrollo , Tiazolidinas/químicaRESUMEN
Microcionamides A (1) and B (2) have been isolated from the Philippine marine sponge Clathria (Thalysias) abietina. These new linear peptides are cyclized via a cystine moiety and have their C-terminus blocked by a 2-phenylethylenamine group. Their total structures, including absolute stereochemistry, were determined by a combination of spectral and chemical methods. Compound 1 was shown to slowly isomerize about the C-36/C-37 double bond when stored in DMSO. Microcionamides A (1) and B (2) exhibited significant cytotoxicity against the human breast tumor cells lines MCF-7 and SKBR-3 and displayed inhibitory activity against Mycobacterium tuberculosis H(37)Ra.