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  • Journal article
    Lu Z, Bergeron JRC, Atkinson RA, Schaller T, Veselkov DA, Oregioni A, Yang Y, Matthews SJ, Malim MH, Sanderson MRet al., 2013,

    Insight into the HIV-1 Vif SOCS-box-ElonginBC interaction

    , Open Biology, Vol: 3, Pages: 1-11, ISSN: 2046-2441

    The HIV-1 viral infectivity factor (Vif) neutralizes cell-encoded antiviral APOBEC3 proteins by recruiting a cellular ElonginB (EloB)/ElonginC (EloC)/Cullin5-containing ubiquitin ligase complex, resulting in APOBEC3 ubiquitination and proteolysis. The suppressors-of-cytokine-signalling-like domain (SOCS-box) of HIV-1 Vif is essential for E3 ligase engagement, and contains a BC box as well as an unusual proline-rich motif. Here, we report the NMR solution structure of the Vif SOCS–ElonginBC (EloBC) complex. In contrast to SOCS-boxes described in other proteins, the HIV-1 Vif SOCS-box contains only one α-helical domain followed by a β-sheet fold. The SOCS-box of Vif binds primarily to EloC by hydrophobic interactions. The functionally essential proline-rich motif mediates a direct but weak interaction with residues 101–104 of EloB, inducing a conformational change from an unstructured state to a structured state. The structure of the complex and biophysical studies provide detailed insight into the function of Vif's proline-rich motif and reveal novel dynamic information on the Vif–EloBC interaction.

  • Journal article
    Clark RI, Tan SWS, Pean CB, Roostalu U, Vivancos V, Bronda K, Pilatova M, Fu J, Walker DW, Berdeaux R, Geissmann F, Dionne MSet al., 2013,

    MEF2 Is an In Vivo Immune-Metabolic Switch

    , CELL, Vol: 155, Pages: 435-447, ISSN: 0092-8674
  • Journal article
    Tulli L, Marchi S, Petracca R, Shaw HA, Fairweather NF, Scarselli M, Soriani M, Leuzzi Ret al., 2013,

    CbpA: a novel surface exposed adhesin of Clostridium difficile targeting human collagen

    , CELLULAR MICROBIOLOGY, Vol: 15, Pages: 1674-1687, ISSN: 1462-5814
  • Journal article
    Dionne MS, 2013,

    Comparative immunology: allorecognition and variable surface receptors outside the jawed vertebrates

    , CURRENT OPINION IN IMMUNOLOGY, Vol: 25, Pages: 608-612, ISSN: 0952-7915
  • Journal article
    Pearson JS, Giogha C, Ong SY, Kennedy CL, Kelly M, Robinson KS, Lung TWF, Mansell A, Riedmaier P, Oates CVL, Zaid A, Muehlen S, Crepin VF, Marches O, Ang C-S, Williamson NA, O'Reilly LA, Bankovacki A, Nachbur U, Infusini G, Webb AI, Silke J, Strasser A, Frankel G, Hartland ELet al., 2013,

    A type III effector antagonizes death receptor signalling during bacterial gut infection

    , NATURE, Vol: 501, Pages: 247-+, ISSN: 0028-0836
  • Journal article
    Andreu N, Zelmer A, Sampson SL, Ikeh M, Bancroft GJ, Schaible UE, Wiles S, Robertson BDet al., 2013,

    Rapid in vivo assessment of drug efficacy against Mycobacterium tuberculosis using an improved firefly luciferase

    , Journal of Antimicrobial Chemotherapy, Vol: 68, Pages: 2118-2127, ISSN: 1460-2091

    Objectives In vivo experimentation is costly and time-consuming, and presents a major bottleneck in anti-tuberculosis drug development. Conventional methods rely on the enumeration of bacterial colonies, and it can take up to 4 weeks for Mycobacterium tuberculosis to grow on agar plates. Light produced by recombinant bacteria expressing luciferase enzymes can be used as a marker of bacterial load, and disease progression can be easily followed non-invasively in live animals by using the appropriate imaging equipment. The objective of this work was to develop a bioluminescence-based mouse model of tuberculosis to assess antibiotic efficacy against M. tuberculosis in vivo.Methods We used an M. tuberculosis strain carrying a red-shifted derivative of the firefly luciferase gene (FFlucRT) to infect mice, and monitored disease progression in living animals by bioluminescence imaging before and after treatment with the frontline anti-tuberculosis drug isoniazid. The resulting images were analysed and the bioluminescence was correlated with bacterial counts.Results Using bioluminescence imaging we detected as few as 1.7 × 103 and 7.5 × 104 reporter bacteria ex vivo and in vivo, respectively, in the lungs of mice. A good correlation was found between bioluminescence and bacterial load in both cases. Furthermore, a marked reduction in luminescence was observed in living mice given isoniazid treatment.Conclusions We have shown that an improved bioluminescent strain of M. tuberculosis can be visualized by non-invasive imaging in live mice during an acute, progressive infection and that this technique can be used to rapidly visualize and quantify the effect of antibiotic treatment. We believe that the model presented here will be of great benefit in early drug discovery as an easy and rapid way to identify active compounds in vivo.

  • Journal article
    Reichmann NT, Cassona CP, Gruendling A, 2013,

    Revised mechanism of D-alanine incorporation into cell wall polymers in Gram-positive bacteria

    , MICROBIOLOGY-SGM, Vol: 159, Pages: 1868-1877, ISSN: 1350-0872
  • Journal article
    Filloux A, 2013,

    MICROBIOLOGY A weapon for bacterial warfare

    , NATURE, Vol: 500, Pages: 284-285, ISSN: 0028-0836
  • Journal article
    Godfray HCJ, Donnelly CA, Kao RR, Macdonald W, McDonald RA, Petrokofsky G, Wood JLN, Woodroffe R, Young DB, McLean ARet al., 2013,

    A restatement of the natural science evidence base relevant to the control of bovine tuberculosis in Great Britain

    , Proceedings of the Royal Society B: Biological Sciences, Vol: 280, ISSN: 0962-8452

    Bovine tuberculosis (bTB) is a very important disease of cattle in Great Britain, where it has been increasing in incidence and geographical distribution. In addition to cattle, it infects other species of domestic and wild animals, in particular the European badger (Meles meles). Policy to control bTB is vigorously debated and contentious because of its implications for the livestock industry and because some policy options involve culling badgers, the most important wildlife reservoir. This paper describes a project to provide a succinct summary of the natural science evidence base relevant to the control of bTB, couched in terms that are as policy-neutral as possible. Each evidence statement is placed into one of four categories describing the nature of the underlying information. The evidence summary forms the appendix to this paper and an annotated bibliography is provided in the electronic supplementary material.

  • Journal article
    Corrigan RM, Gruendling A, 2013,

    Cyclic di-AMP: another second messenger enters the fray

    , NATURE REVIEWS MICROBIOLOGY, Vol: 11, Pages: 513-524, ISSN: 1740-1526

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