Synthesis of 3-O-methylviridicatin analogues with improved anti-TNF-alpha properties

We synthesized 3-O-methylviridicatin and several analogues of this fungal metabolite. We showed that replacement of the methoxy moiety by a thiomethyl enhanced dramatically its ability to inhibit TNF-alpha secretion. These results strongly suggest that 4-phenyl-3-methylthioquinolinone may provide the basis for the development of new anti-inflammatory agents.     

Genome structural variation discovery and genotyping

Comparisons of human genomes show that more base pairs are altered as a result of structural variation - including copy number variation - than as a result of point mutations. Here we review advances and challenges in the discovery and genotyping of structural variation. The recent application of massively parallel sequencing methods has complemented microarray-based methods and has led to an exponential increase in the discovery of smaller structural-variation events. Some global discovery biases remain, but the integration of experimental and computational approaches is proving fruitful for accurate characterization of the copy, content and structure of variable regions. We argue that the long-term goal should be routine, cost-effective and high quality de novo assembly of human genomes to comprehensively assess all classes of structural variation.     

Complete genome sequence of Bacteroides helcogenes type strain (P 36-108)

Bacteroides helcogenes Benno et al. 1983 is of interest because of its isolated phylogenetic location and, although it has been found in pig feces and is known to be pathogenic for pigs, occurrence of this bacterium is rare and it does not cause significant damage in intensive animal husbandry. The genome of B. helcogenes P 36-108(T) is already the fifth completed and published type strain genome from the genus Bacteroides in the family Bacteroidaceae. The 3,998,906 bp long genome with its 3,353 protein-coding and 83 RNA genes consists of one circular chromosome and is a part of the Genomic Encyclopedia of Bacteria and Archaea project.     

Rhizobial migration toward roots mediated by FadL-ExoFQP modulation of extracellular long-chain AHLs

Migration from rhizosphere to rhizoplane is a key selecting process in root microbiome assembly, but not fully understood. Rhizobiales members are overrepresented in the core root microbiome of terrestrial plants, and here we report a genome-wide transposon-sequencing of rhizoplane fitness genes of beneficial Sinorhizobium fredii on wild soybean, cultivated soybean, rice, and maize. There were few genes involved in broad-host-range rhizoplane colonization. The fadL mutant lacking a fatty acid transporter exhibited high colonization rates, while mutations in exoFQP (encoding membrane proteins directing exopolysaccharide polymerization and secretion), but not those in exo genes essential for exopolysaccharide biosynthesis, led to severely impaired colonization rates. This variation was not explainable by their rhizosphere and rhizoplane survivability, and associated biofilm and exopolysaccharide production, but consistent with their migration ability toward rhizoplane, and associated surface motility and the mixture of quorum-sensing AHLs (N-acylated-L-homoserine lactones). Genetics and physiology evidences suggested that FadL mediated long-chain AHL uptake while ExoF mediated the secretion of short-chain AHLs which negatively affected long-chain AHL biosynthesis. The fadL and exoF mutants had elevated and depleted extracellular long-chain AHLs, respectively. A synthetic mixture of long-chain AHLs mimicking that of the fadL mutant can improve rhizobial surface motility. When this AHL mixture was spotted into rhizosphere, the migration toward roots and rhizoplane colonization of S. fredii were enhanced in a diffusible way. This work adds novel parts managing extracellular AHLs, which modulate bacterial migration toward rhizoplane. The FadL-ExoFQP system is conserved in Alphaproteobacteria and may shape the “home life” of diverse keystone rhizobacteria.Subject terms: Microbial ecology, Functional genomics, Bacterial genetics