538 research outputs found

    Plasticity of streptomyces coelicolor membrane composition under different growth conditions and during development

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    Streptomyces coelicolor is a model actinomycete that is well known for the diversity of its secondary metabolism and its complex life cycle. As a soil inhabitant, it is exposed to heterogeneous and frequently changing environmental circumstances. In the present work, we studied the effect of diverse growth conditions and phosphate depletion on its lipid profile and the relationship between membrane lipid composition and development in S. coelicolor. The lipid profile from cultures grown on solid media, which is closer to the natural habitat of this microorganism, does not resemble the previously reported lipid composition from liquid grown cultures of S. coelicolor. Wide variations were also observed across different media, growth phases, and developmental stages indicating active membrane remodeling. Ornithine lipids (OL) are phosphorus-free polar lipids that were accumulated mainly during sporulation stages, but were also major components of the membrane under phosphorus limitation. In contrast, phosphatidylethanolamine, which had been reported as one of the major polar lipids in the genus Streptomyces, is almost absent under these conditions. We identified one of the genes responsible for the synthesis of OL (SCO0921) and found that its inactivation causes the absence of OL, precocious morphological development and actinorhodin production. Our observations indicate a remarkable plasticity of the membrane composition in this bacterial species, reveal a higher metabolic complexity than expected, and suggest a relationship between cytoplasmic membrane components and the differentiation programs in S. coelicolor

    Finding the Missing Links among Metabolites, Microbes, and the Host

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    The unexpected diversity of the human microbiome and metabolome far exceeds the complexity of the human genome. Although we now understand microbial taxonomic and genetic repertoires in some populations, we are just beginning to assemble the necessary computational and experimental tools to understand the metabolome in comparable detail. However, even with the limited current state of knowledge, individual connections between microbes and metabolites, between microbes and immune function, and between metabolites and immune function are being established. Here, we provide our perspective on these connections and outline a systematic research program that could turn these individual links into a broader network that allows us to understand how these components interact. This program will enable us to exploit connections among the microbiome, metabolome, and host immune system to maintain health and perhaps help us understand how to reverse the processes that lead to a wide range of immune and other diseases

    Enhanced Characterization of Drug Metabolism and the Influence of the Intestinal Microbiome: A Pharmacokinetic, Microbiome, and Untargeted Metabolomics Study.

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    Determining factors that contribute to interindividual and intra-individual variability in pharmacokinetics (PKs) and drug metabolism is essential for the optimal use of drugs in humans. Intestinal microbes are important contributors to variability; however, such gut microbe-drug interactions and the clinical significance of these interactions are still being elucidated. Traditional PKs can be complemented by untargeted mass spectrometry coupled with molecular networking to study the intricacies of drug metabolism. To show the utility of molecular networking on metabolism we investigated the impact of a 7-day course of cefprozil on cytochrome P450 (CYP) activity using a modified Cooperstown cocktail and assessed plasma, urine, and fecal data by targeted and untargeted metabolomics and molecular networking in healthy volunteers. This prospective study revealed that cefprozil decreased the activities of CYP1A2, CYP2C19, and CYP3A, decreased alpha diversity and increased interindividual microbiome variability. We further demonstrate a relationship between the loss of microbiome alpha diversity caused by cefprozil and increased drug and metabolite formation in fecal samples. Untargeted metabolomics/molecular networking revealed several omeprazole metabolites that we hypothesize may be metabolized by both CYP2C19 and bacteria from the gut microbiome. Our observations are consistent with the hypothesis that factors that perturb the gut microbiome, such as antibiotics, alter drug metabolism and ultimately drug efficacy and toxicity but that these effects are most strongly revealed on a per individual basis

    Specialized Metabolites from the Microbiome in Health and Disease

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    The microbiota, and the genes that comprise its microbiome, play key roles in human health. Host-microbe interactions affect immunity, metabolism, development, and behavior, and dysbiosis of gut bacteria contributes to disease. Despite advances in correlating changes in the microbiota with various conditions, specific mechanisms of host-microbiota signaling remain largely elusive. We discuss the synthesis of microbial metabolites, their absorption, and potential physiological effects on the host. We propose that the effects of specialized metabolites may explain present knowledge gaps in linking the gut microbiota to biological host mechanisms during initial colonization, and in health and disease
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