c-di-AMP: An essential molecule in the signaling pathways that regulate the viability and virulence of gram-positive bacteria

Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an attractive antimicrobial drug target and therefore has been the focus of intensive study in several important pathogens

Stress and immunological evaluations of sea urchin treated with four different nutraceuticals

Sea urchins have been considered as delicacy for many years in different regions of the world. Recently, their importance is increasing in the research labs for not only to produce quality gonads for delicacy but to produce pharmaceuticals from them. As they are gaining importance, many people are trying to grow them in aquaculture but due to inadequate knowledge of farming of sea urchins, quality production has not yet been achieved. Some factors such as handling, salinity, and crowding cause stress to sea urchin during aquaculture and stress makes animal susceptible to diseases and also leads to low yield and low quality products. The sea urchin product quality is being determined by the color, texture, freshness and taste of their gonads. Since stress is causing loss to the aquaculture, it is important to identify the cause of stress, determine the stress responses and find possible solution to minimize stress. To investigate the stress responses in sea urchins, physiological and immunological responses against handling were studied in Arbacia punctulata, a purple sea urchin reared in recirculatory system in the lab. For this study, sea urchins were obtained and acclimated for two weeks in optimal conditions. The experiments, then, were conducted for five weeks and the animals were sampled at the end of five weeks. Sea urchins were reared in aquaculture system in different groups - stressed and unstressed, treated with four different feed [control feed (salmon feed) and hydrogenated coconut oil (HCO)-supplemented salmon feed, sunflower oil (SO) -supplemented salmon feed and linseed oil (LO)-supplemented salmon feed]. For this study, sea urchins were obtained and acclimated for two weeks in optimal conditions. The experiments, then, were conducted for five weeks and the animals were sampled at the end of five weeks. Condition factors, gonado-somatic index, packed cell volume, coelomic fluid protein, total and differential cell counts, coelomocyte phagocytic capacity, and respiratory burst activity were observed to measure the stress and immune responses. The results from these experiments showed that handling induces significant physiological and immunological stress responses. Stressed groups showed higher packed cell volume, higher gonado-somatic indices, higher number of total and differential cell counts, lower phagocytic and respiratory bust activities compared to the unstressed sea urchins. Sea urchin groups treated with specific nutraceuticals showed significant variations in their stress responses. In this study, nutraceutical treated groups had lower stress responses than the control feed groups, and among the nutraceutical treated group linseed oil (LO) treated groups had better effects in minimizing stress among all the groups