Role of glyoxylate shunt in oxidative stress response [Microbiology]

April 1st, 2016 by Ahn, S., Jung, J., Jang, I.-A., Madsen, E. L., Park, W.

The glyoxylate shunt (GS) is a two-step metabolic pathway (isocitrate lyase, aceA; and malate synthase, glcB) that serves as an alternative to the TCA cycle. The GS bypasses the carbon dioxide-producing steps of the TCA cycle and is essential for acetate and fatty acid metabolism in bacteria. GS can be upregulated under conditions of oxidative stress, antibiotic stress, and host infection, which implies that it plays important but poorly explored roles in stress defense and pathogenesis. In many bacterial species, including Pseudomonas aeruginosa, aceA and glcB are not in an operon, unlike in Escherichia coli. In P. aeruginosa, we explored relationships between GS genes and growth, transcription profiles, and biofilm formation. Contrary to our expectations, deletion of aceA in P. aeruginosa improved cell growth under conditions of oxidative and antibiotic stress. Transcriptome data suggested that aceA mutants underwent a metabolic shift toward aerobic denitrification; this was supported by additional evidence, including upregulation of denitrification-related genes, decreased oxygen consumption without lowering ATP yield, increased production of denitrification intermediates (NO and N2O), and increased cyanide resistance. The aceA mutants also produced a thicker exopolysaccharide layer: a phenotype consistent with aerobic denitrification. A bioinformatic survey across known bacterial genomes showed that only microorganisms capable of aerobic metabolism possess the glyoxylate shunt. This trend is consistent with the hypothesis that the GS plays a previously unrecognized role in allowing bacteria to tolerate oxidative stress.

Entry of Bluetongue virus capsid requires the late endosomal specific lipid lysobisphosphatidic acid [Lipids]

April 1st, 2016 by Patel, A., Mohl, B.-P., Roy, P.

The entry of viruses into host cells is one of the key processes for the infection.. The mechanisms of cellular entry for enveloped virus have been well studied. The fusion proteins as well as the facilitating cellular lipid factors involved in the viral fusion entry process have been well characterized. The process of non-enveloped virus cell entry, in comparison, remains poorly defined, particularly for large complex capsid viruses of the family Reoviridae, which comprises a range of mammalian pathogens. These viruses enter cells without the aid of a limiting membrane and thus cannot fuse with host cell membranes to enter cells. Instead, these viruses are believed to penetrate membranes of the host cell during endocytosis. However, the molecular mechanism of this process is largely undefined. Here we show utilizing an in vitro liposome penetration assay and cell biology that Bluetongue virus (BTV), an archetypal member of the Reoviridae, utilizes the late endosomal specific lipid lysobisphosphatidic acid (LBPA) for productive membrane penetration and viral entry. Further we provide preliminary evidence that LBPA facilitates pore expansion during membrane penetration suggesting a mechanism for lipid factor requirement of BTV. This data indicates that despite the lack of a membrane envelope, the entry process of BTV is similar in specific lipid requirements to enveloped viruses that enter cells through the late endosome. These results are the first, to our knowledge, to demonstrate that a large non-enveloped virus of the Reoviridae has specific lipid requirements for membrane penetration and host cell entry.

Essential biphasic role for JAK3 catalytic activity in IL-2 receptor signaling

March 28th, 2016 by Geoffrey A Smith

Nature Chemical Biology 12, 373 (2016). doi:10.1038/nchembio.2056

Authors: Geoffrey A Smith, Kenji Uchida, Arthur Weiss & Jack Taunton

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AIG1 and ADTRP are atypical integral membrane hydrolases that degrade bioactive FAHFAs

March 28th, 2016 by William H Parsons

Nature Chemical Biology 12, 367 (2016). doi:10.1038/nchembio.2051

Authors: William H Parsons, Matthew J Kolar, Siddhesh S Kamat, Armand B Cognetta III, Jonathan J Hulce, Enrique Saez, Barbara B Kahn, Alan Saghatelian & Benjamin F Cravatt

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Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification

March 28th, 2016 by Richard M Deans

Nature Chemical Biology 12, 361 (2016). doi:10.1038/nchembio.2050

Authors: Richard M Deans, David W Morgens, Ayşe Ökesli, Sirika Pillay, Max A Horlbeck, Martin Kampmann, Luke A Gilbert, Amy Li, Roberto Mateo, Mark Smith, Jeffrey S Glenn, Jan E Carette, Chaitan Khosla & Michael C Bassik

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Chemically Modifying Viruses for Diverse Applications

March 21st, 2016 by Kritika Mohan and Gregory A. Weiss

TOC Graphic

ACS Chemical Biology
DOI: 10.1021/acschembio.6b00060

Why Nature Chose Selenium

March 21st, 2016 by Hans J. Reich and Robert J. Hondal

TOC Graphic

ACS Chemical Biology
DOI: 10.1021/acschembio.6b00031

Steric trapping reveals a cooperativity network in the intramembrane protease GlpG

March 21st, 2016 by Ruiqiong Guo

Nature Chemical Biology 12, 353 (2016). doi:10.1038/nchembio.2048

Authors: Ruiqiong Guo, Kristen Gaffney, Zhongyu Yang, Miyeon Kim, Suttipun Sungsuwan, Xuefei Huang, Wayne L Hubbell & Heedeok Hong

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Exploiting nongenetic cell-to-cell variation for enhanced biosynthesis

March 21st, 2016 by Yi Xiao

Nature Chemical Biology 12, 339 (2016). doi:10.1038/nchembio.2046

Authors: Yi Xiao, Christopher H Bowen, Di Liu & Fuzhong Zhang

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Malic enzyme tracers reveal hypoxia-induced switch in adipocyte NADPH pathway usage

March 21st, 2016 by Ling Liu

Nature Chemical Biology 12, 345 (2016). doi:10.1038/nchembio.2047

Authors: Ling Liu, Supriya Shah, Jing Fan, Junyoung O Park, Kathryn E Wellen & Joshua D Rabinowitz

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