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  • 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
    Mikkelsen H, Hui K, Barraud N, Filloux Aet al., 2013,

    The pathogenicity island encoded PvrSR/RcsCB regulatory network controls biofilm formation and dispersal in Pseudomonas aeruginosa PA14

    , Molecular Microbiology, Vol: 89, Pages: 450-463, ISSN: 0950-382X

    Pseudomonas aeruginosa biofilm formation is linked to persistent infections in humans. Biofilm formation is facilitated by extracellular appendages, some of which are assembled by the Chaperone Usher Pathway (Cup). The cupD gene cluster is located on the PAPI‐1 pathogenicity island of strain PA14 and has probably been acquired together with four genes encoding two‐component signal transduction proteins. We have previously showed that the RcsB response regulator activates expression of the cupD genes, which leads to the production of CupD fimbriae and increased attachment. Here we show that RcsB activity is tightly modulated by two sensors, RcsC and PvrS. While PvrS acts as a kinase that enhances RcsB activity, RcsC has a dual function, first as a phosphorelay, and second as a phosphatase. We found that, under certain growth conditions, overexpression of RcsB readily induces biofilm dispersal. Microarray analysis shows that RcsB positively controls expression of pvrR that encodes the phosphodiesterase required for this dispersal process. Finally, in addition to the PAPI‐1 encoded cupD genes, RcsB controls several genes on the core genome, some of which encode orphan response regulators. We thus discovered that RcsB is central to a large regulatory network that fine‐tunes the switch between biofilm formation and dispersal.
  • 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
  • Journal article
    Collins JW, Meganck JA, Kuo C, Francis KP, Frankel Get al., 2013,

    4D Multimodality Imaging of <i>Citrobacter rodentium</i> Infections in Mice

    , JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, ISSN: 1940-087X
  • Journal article
    Raymond B, Young JC, Pallett M, Endres RG, Clements A, Frankel Get al., 2013,

    Subversion of trafficking, apoptosis, and innate immunity by type III secretion system effectors

    , TRENDS IN MICROBIOLOGY, Vol: 21, Pages: 430-439, ISSN: 0966-842X
  • Journal article
    Santos AJM, Meinecke M, Fessler MB, Holden DW, Boucrot Eet al., 2013,

    Preferential invasion of mitotic cells by Salmonella reveals that cell surface cholesterol is maximal during metaphase

    , JOURNAL OF CELL SCIENCE, Vol: 126, Pages: 2990-2996, ISSN: 0021-9533
  • Journal article
    Larrouy-Maumus G, Biswas T, Hunt DM, Kelly G, Tsodikov OV, de Carvalho LPSet al., 2013,

    Discovery of a glycerol 3-phosphate phosphatase reveals glycerophospholipid polar head recycling in <i>Mycobacterium tuberculosis</i>

    , PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 110, Pages: 11320-11325, ISSN: 0027-8424
  • Journal article
    Krishnan N, Robertson BD, Thwaites G, 2013,

    Pathways of IL-1β secretion by macrophages infected with clinical Mycobacterium tuberculosis strains

    , Tuberculosis, Vol: 93, Pages: 538-547, ISSN: 1873-281X

    The pro-inflammatory cytokine IL-1β is a key mediator of inflammation and plays an important role in the host resistance to Mycobacterium tuberculosis infections. To date, most studies have examined the mechanisms of IL-1β secretion using laboratory strains of M. tuberculosis and the findings may not be widely applicable to contemporary clinical strains. Here, we investigated the primary pathways of IL-1β secretion in macrophages infected with a panel of 17 clinical M. tuberculosis isolates, representing Euro-American, Indo-Oceanic and East-Asian/Beijing lineages. Our aim was to dissect the pathways involved in M. tuberculosis induced IL-1β secretion and to determine whether they are common to all clinical isolates. We found that the isolates were capable of eliciting variable concentrations of IL-1β from infected murine macrophages, but this phenomenon could not be attributed to differential IL-1β mRNA transcription or pro-IL-1β accumulation. We demonstrate that viable bacteria are required to induce IL-1β secretion from macrophages, but IL-1β secretion was only partially abrogated by caspase-1 inhibition. Almost complete IL-1β secretion inhibition was produced with combined caspase-1 and some serine protease inhibitors. Taken together, these findings demonstrate that clinical strains of M. tuberculosis employ a unique caspase-1 independent pathway to stimulate IL-1β secretion from macrophages.
  • Journal article
    Williams KJ, Bryant WA, Jenkins VA, Barton GR, Witney AA, Pinney JW, Robertson BDet al., 2013,

    Deciphering the response of Mycobacterium smegmatis to nitrogen stress using bipartite active modules

    , BMC Genomics, Vol: 14, ISSN: 1471-2164

    BackgroundThe ability to adapt to environments with fluctuating nutrient availability is vital for bacterial survival. Although essential for growth, few nitrogen metabolism genes have been identified or fully characterised in mycobacteria and nitrogen stress survival mechanisms are unknown.ResultsA global transcriptional analysis of the mycobacterial response to nitrogen stress, showed a significant change in the differential expression of 16% of the Mycobacterium smegmatis genome. Gene expression changes were mapped onto the metabolic network using Active Modules for Bipartite Networks (AMBIENT) to identify metabolic pathways showing coordinated transcriptional responses to the stress. AMBIENT revealed several key features of the metabolic response not identified by KEGG enrichment alone. Down regulated reactions were associated with the general reduction in cellular metabolism as a consequence of reduced growth rate. Up-regulated modules highlighted metabolic changes in nitrogen assimilation and scavenging, as well as reactions involved in hydrogen peroxide metabolism, carbon scavenging and energy generation.ConclusionsApplication of an Active Modules algorithm to transcriptomic data identified key metabolic reactions and pathways altered in response to nitrogen stress, which are central to survival under nitrogen limiting environments.
  • Journal article
    Harding CR, Stoneham CA, Schuelein R, Newton H, Oates CV, Hartland EL, Schroeder GN, Frankel Get al., 2013,

    The Dot/Icm Effector SdhA Is Necessary for Virulence of <i>Legionella pneumophila</i> in <i>Galleria mellonella</i> and A/J Mice

    , INFECTION AND IMMUNITY, Vol: 81, Pages: 2598-2605, ISSN: 0019-9567

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