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• 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
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  • Citations: 98
• 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
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  • Citations: 29
• 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
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  • Citations: 41
• 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.

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• 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.

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• 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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  • Citations: 34
• Journal article
  Tsolaki AG, Nagy J, Leiva S, Kishore U, Rosenkrands I, Robertson BDet al., 2013,

  <i>Mycobacterium tuberculosis</i> antigen 85B and ESAT-6 expressed as a recombinant fusion protein in <i>Mycobacterium smegmatis</i> elicits cell-mediated immune response in a murine vaccination model

  , MOLECULAR IMMUNOLOGY, Vol: 54, Pages: 278-283, ISSN: 0161-5890
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  • Citations: 8
• Journal article
  Chen K, d'Arc S, Setty N, Bamford K, Fairweather N, Tyrrell-Price Jet al., 2013,

  In Recurrent <i>C</i>. <i>difficile</i>, the CRP Response to the Primary <i>C</i>. <i>difficile</i> Infection Predicts Whether the Same Strain or a Different Strain will Cause a Second Infection

  , DIGESTIVE DISEASES AND SCIENCES, Vol: 58, Pages: 1683-1688, ISSN: 0163-2116
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  • Citations: 3
• Journal article
  Dembek M, Stabler RA, Witney AA, Wren BW, Fairweather NFet al., 2013,

  Transcriptional analysis of temporal gene expression in germinating clostridium difficile 630 endospores

  , PLOS One, Vol: 8, ISSN: 1932-6203

  Clostridium difficile is the leading cause of hospital acquired diarrhoea in industrialised countries. Under conditions that are not favourable for growth, the pathogen produces metabolically dormant endospores via asymmetric cell division. These are extremely resistant to both chemical and physical stress and provide the mechanism by which C. difficile can evade the potentially fatal consequences of exposure to heat, oxygen, alcohol, and certain disinfectants. Spores are the primary infective agent and must germinate to allow for vegetative cell growth and toxin production. While spore germination in Bacillus is well understood, little is known about C. difficile germination and outgrowth. Here we use genome-wide transcriptional analysis to elucidate the temporal gene expression patterns in C. difficile 630 endospore germination. We have optimized methods for large scale production and purification of spores. The germination characteristics of purified spores have been characterized and RNA extraction protocols have been optimized. Gene expression was highly dynamic during germination and outgrowth, and was found to involve a large number of genes. Using this genome-wide, microarray approach we have identified 511 genes that are significantly up- or down-regulated during C. difficile germination (p≤0.01). A number of functional groups of genes appeared to be co-regulated. These included transport, protein synthesis and secretion, motility and chemotaxis as well as cell wall biogenesis. These data give insight into how C. difficile re-establishes its metabolism, re-builds the basic structures of the vegetative cell and resumes growth.

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• Journal article
  Leen EN, Kwok KYR, Birtley JR, Simpson PJ, Subba-Reddy CV, Chaudhry Y, Sosnovtsev SV, Green KY, Prater SN, Tong M, Young JC, Chung LMW, Marchant J, Roberts LO, Kao CC, Matthews S, Goodfellow IG, Curry Set al., 2013,

  Structures of the Compact Helical Core Domains of Feline Calicivirus and Murine Norovirus VPg Proteins

  , JOURNAL OF VIROLOGY, Vol: 87, Pages: 5318-5330, ISSN: 0022-538X
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  • Citations: 36

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