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Interleukin-17 (IL-17)-secreting T cells of the T helper 17 ([T.sub.H]17) lineage play a pathogenic role in multiple inflammatory and autoimmune conditions and thus represent a highly attractive target for therapeutic intervention. We report that inhibition of acetyl-CoA carboxylase 1 (ACC1) restrains the formation of human and mouse [T.sub.H]17 cells and promotes the development of anti-inflammatory Foxp[3.sup.+] regulatory T ([T.sub.reg]) cells. We show that [T.sub.H]17 cells, but not [T.sub.reg] cells, depend on ACC1-mediated de novo fatty acid synthesis and the underlying glycolytic-lipogenic metabolic pathway for their development. Although [T.sub.H]17 cells use this pathway to produce phospholipids for cellular membranes, [T.sub.reg] cells readily take up exogenous fatty acids for this purpose. Notably, pharmacologic inhibition or T cell-specific deletion of ACC1 not only blocks de novo fatty acid synthesis but also interferes with the metabolic flux of glucose-derived carbon via glycolysis and the tricarboxylic acid cycle. In vivo, treatment with the ACC-specific inhibitor soraphen A or T cell-specific deletion of ACC1 in mice attenuates [T.sub.H]17 cell-mediated autoimmune disease. Our results indicate fundamental differences between [T.sub.H]17 cells and [T.sub.reg] cells regarding their dependency on ACC1-mediated de novo fatty acid synthesis, which might be exploited as a new strategy for metabolic immune modulation of [T.sub.H]17 cell-mediated inflammatory diseases., To develop from naive cells into distinct T cell lineages, activated T cells undergo a massive metabolic switch to cope with the demands of cell growth and multiple rounds of [...]

Basic processes of the fatty acid metabolism have an important impact on the function of intestinal epithelial cells (IEC). However, while the role of cellular fatty acid oxidation is well appreciated, it is not clear how de novo fatty acid synthesis (FAS) influences the biology of IECs. We report here that interfering with de novo FAS by deletion of the enzyme Acetyl-CoA-Carboxylase (ACC)1 in IECs results in the loss of epithelial crypt structures and a specific decline in Lgr5+ intestinal epithelial stem cells (ISC). Mechanistically, ACC1-mediated de novo FAS supports the formation of intestinal organoids and the differentiation of complex crypt structures by sustaining the nuclear accumulation of PPARδ/β-catenin in ISCs. The dependency of ISCs on cellular de novo FAS is tuned by the availability of environmental lipids, as an excess delivery of external fatty acids is sufficient to rescue the defect in crypt formation. Finally, inhibition of ACC1 reduces the formation of tumors in colitis-associated colon cancer, together highlighting the importance of cellular lipogenesis for sustaining ISC function and providing a potential perspective to colon cancer therapy. Here the authors report that inhibition of de novo fatty acid synthesis by deleting the enzyme Acetyl-CoA-Carboxylase 1 in the intestinal epithelium results in the loss of crypt structures and a specific decline in Lgr5+ intestinal epithelial stem cells. [ABSTRACT FROM AUTHOR]

A study on the discrimination of the stable carbon isotopes by different microorganisms were made to determine whether ratios of carbon isotopes in microbial lipids can be used as indicators of substrate usage. Eleven strains of well known bacterial and fungal species with four different isotopically define carbon sources were grown and their isotope ratios of fatty acids of different lipid fractions were identified. Results show that the isotope ratio does not depend on the growth stage.

A study was conducted to isolate a novel fatty acid from the coryneform bacterial strain LMG 3820. A set of nuclear magnetic resonance data was utilized to determine the nature and substitution patterns of the glycerol moieties. Results indicated that different organisms supporting 16S rDNA sequences accommodate various fatty acid and lipid compositions. Findings also showed that the fatty acid's routine detection is influenced by the equivalent chain number.

High-pressure liquid chromatography was used to monitor N-cyclohexyldiazenium dioxide (HDO) concentration in isotope-labeled ([super 13]C) and nonlabeled ([super 12]C) Cu-HDO incorporated in wood sawdust mixed with soil. Cu-HDO as part of a wood preservative was observed to effectively decrease fungal wood decay and overall microbial respiration from soil.

The spatial and compositional structure and complex dynamics of the developing biofilm and its polychlorinated biphenyls (PCB)-degrading activity, leading to the identification of three stages of biofilm development is reported. The biofilm developing from PCB-contaminated soil on PCB droplets displayed a pronounced pattern of maturation not reported before from pure-culture experiments.

Fungi are present in the most diverse environments including the interior of plant tissues, living as endophytes without causing apparent damage. These endophytes are producers of secondary metabolites, also known as natural products, such as fungicides. Here, we evaluated the ethyl acetate fractions obtained from endophytic fungi isolated from plants in the genus Begonia. The fractions were submitted to inhibitory test against the plant pathogens Diaporthe phaseolorum and Colletotrichum gloeosporioides. From the 88 ethyl acetate fractions evaluated, 14.7 % inhibited C. gloeosporioides and 11.3 % inhibited D. phaseolorum. One fungal isolate displaying an active fraction was selected for chemical investigation. The fungus identified as Neopestalotiopsis sp., produced a compound that was active against D. phaseolorum, with a MIC of 312 µg mL-1 (1,695.3 µM). The compound was identified by mass spectrometry and ¹H NMR as the known compound fumiquinone B. The results highlight that the endophytes are capable of producing compounds that may be used to control plant pathogens. The compound fumiquinone B is reported for the first time as an antifungal agent against D. phaseolorum, a relevant plant pathogen worldwide. This is also the first report of the production of fumiquinone B by the genus Neopestalotiopsis. [ABSTRACT FROM AUTHOR]

Treating infections organized in biofilms is a challenge due to the resistance of the pathogens against antibiotics and host immune cells. Many fungi grow in a wet environment, favorable for the growth of bacterial biofilms, and we speculated that fungi possess some strategies to control these bacterial biofilms. A fungus identified as Hypoxylon fragiforme, was collected in the Harz Mountains, Germany, and its mycelial culture was fermented in different culture media for 67 days to test its biological potential against bacterial biofilms. Sclerin, sclerin diacid and its 3-methyl monoester (methyl 1-(5-hydroxy-6-carboxylic-2,3,4-trimethylphenyl) propionate) are here described for the first time from this fungus. Sclerin and its diacid interfered with the biofilm formation of the pathogen Staphylococcus aureus, inhibiting 86% and 80% of the biofilm at 256 μg mL-1, respectively, but not killing the bacterium. Interestingly, the monomethylester of sclerin diacid was inactive. Although these compounds did not possess any activity against a pre-formed biofilm, they prevented its formation at subtoxic concentrations. Furthermore, sclerin and its diacid displayed a high specificity against Staphylococcus aureus, indicating a good strategy against pathogenic biofilms when combined with antibiotics. [ABSTRACT FROM AUTHOR]

In the version of this article initially published online, the number 21.45, corresponding to the percentage of cells, was missing from the bottom right quadrant of the flow cytometry plot [...]