Burkholderia cenocepacia ET12 strain activates TNFR1 signalling in cystic fibrosis airway epithelial cells

Burkholderia cenocepacia is an important pulmonary pathogen in individuals with cystic fibrosis (CF). Infection is often associated with severe pulmonary inflammation, and some patients develop a fatal necrotizing pneumonia and sepsis (‘cepacia syndrome’). The mechanisms by which this species causes severe pulmonary inflammation are poorly understood. Here, we demonstrate that B. cenocepacia BC7, a potentially virulent representative of the epidemic ET12 lineage, binds to tumour necrosis factor receptor 1 (TNFR1) and activates TNFR1-related signalling pathway similar to TNF-α, a natural ligand for TNFR1. This interaction participates in stimulating a robust IL-8 production from CF airway epithelial cells. In contrast, BC45, a less virulent ET12 representative, and ATCC 25416, an environmental B. cepacia strain, do not bind to TNFR1 and stimulate only minimal IL-8 production from CF cells. Further, TNFR1 expression is increased in CF airway epithelial cells compared with non-CF cells. We also show that B. cenocepacia ET12 strain colocaizes with TNFR1 in vitro and in the lungs of CF patients who died due to infection with B. cenocepacia, ET12 strain. Together, these results suggest that interaction of B. cenocepacia , ET12 strain with TNFR1 may contribute to robust inflammatory responses elicited by this organism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73011/1/j.1462-5822.2007.01029.x.pd

AraGEM, a Genome-scale reconstruction of the primary metabolic network in arabidopsis

Genome-scale metabolic network models have been successfully used to describe metabolism in a variety of microbial organisms as well as specific mammalian cell types and organelles. This systems-based framework enables the exploration of global phenotypic effects of gene knockouts, gene insertion, and up-regulation of gene expression. We have developed a genome-scale metabolic network model (AraGEM) covering primary metabolism for a compartmentalized plant cell based on the Arabidopsis (Arabidopsis thaliana) genome. AraGEM is a comprehensive literature-based, genome-scale metabolic reconstruction that accounts for the functions of 1,419 unique open reading frames, 1,748 metabolites, 5,253 gene-enzyme reaction-association entries, and 1,567 unique reactions compartmentalized into the cytoplasm, mitochondrion, plastid, peroxisome, and vacuole. The curation process identified 75 essential reactions with respective enzyme associations not assigned to any particular gene in the Kyoto Encyclopedia of Genes and Genomes or AraCyc. With the addition of these reactions, AraGEM describes a functional primary metabolism of Arabidopsis. The reconstructed network was transformed into an in silico metabolic flux model of plant metabolism and validated through the simulation of plant metabolic functions inferred from the literature. Using efficient resource utilization as the optimality criterion, AraGEM predicted the classical photorespiratory cycle as well as known key differences between redox metabolism in photosynthetic and nonphotosynthetic plant cells. AraGEM is a viable framework for in silico functional analysis and can be used to derive new, nontrivial hypotheses for exploring plant metabolism