读“Detection of Burkholderia pseudomallei toxin-mediated inhibition of protein synthesis using a Caenorhabditis elegans ugt-29 biosensor”

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Burkholderia pseudomallei is a Gram-negative saprophytic soil bacterium, the causative agent for meloidosis, which results in high mortality in human. Despite theextensive research about the pathogeny for this bacterium, there are still manyvirulent factors of Burkholderia pseudomallei remained unclear. In theirprevious study, the researchers found that 6% in genome of B. psedomallei infected Caenorhabditis elegans, a widely used nematode biosensor for xenobiotic chemicals from food and environment, have been modulated as a host response to the infection. Among these genes, majority were involved in the detoxification enzyme family, thus the results proposed the importance of toxin molecules in the pathogenesis of B. psedomallei. However, up to date, only limited toxin molecules from B. psedomallei are identified. In this research, researchers tried to identify the toxin molecule(s) which induced the robust up-regulation of ugt-29 gene,which encodes ugt-29 protein for detoxification during the infection process, in the infected C. elegans. In order to do this, the researchers construct a C.elegans ugt-29 gene Green Fluorescence Protein reporter, when ugt-29 protein is expressed, the nematode will show green fluorescence. The first step they confirmed that the ugt-29 expression is ubiquitous in the worm when invaded by the bacterium. Then, they need to figure out that whether ugt-29 expression is unique to B.psedomallei. They exposed the worms to four other Burkholderia species and three other non-Burkholderia pathogens. The results indicated that only Burkholderia species infected C. elegans show strong green fluorescence and the intensity is dependent on the bacterial virulence. The authors noted that the zip-2 signaling pathway regulates ugt-29 gene,they using a double mutant worm and RNAi technique have confirmed that the ZIP-2 enforces the ugt-29 expression and increase the survival of the worms. Recent studies identified the zip-2 signaling pathway is a surveillance system used by nematode to monitor the integrity of corecellular activities. In the light of transcriptional regulation, the author wondered if toxins or bacterial virulence factors caused the cellular perturbation whilst zip-2 signaling pathway is in response to the toxin(s) or factor(s). The researchers proved that the over expression of ugt-29 is inresponse to the inhibition of host protein synthesis no matter the inhibitor is biological or abiotic. After they confirm the existence of the toxin factor(s) involved in the pathogenesis process of B. psedomallei,they analyzed the secretion products of three different Burkholderia strains by liquid chromatograph-massspectrometry (LC-MS). This product should be produced by B. psedomallei and B. cepacia but absent in B. thailandensis. They found 36 such chemicals and these chemicals are not proteins. They indicated that the most effective chemical induced the over expression of ugt-29 is bactobolin.

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