@article{DembekBarquistBoinettetal.2015,
  author    = {Dembek, Marcin and Barquist, Lars and Boinett, Christine J. and Cain, Amy K. and Mayho, Matthew and Lawley, Trevor D. and Fairweather, Neil F. and Fagan, Robert P.},
  title     = {High-throughput analysis of gene essentiality and sporulation in Clostridium difficile},
  series = {mBio},
  volume    = {6},
  journal   = {mBio},
  number    = {2},
  doi       = {10.1128/mBio.02383-14},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143745},
  pages     = {e02383-14},
  year      = {2015},
  abstract  = {Clostridium difficile is the most common cause of antibiotic-associated intestinal infections and a significant cause of morbidity and mortality. Infection with C. difficile requires disruption of the intestinal microbiota, most commonly by antibiotic usage. Therapeutic intervention largely relies on a small number of broad-spectrum antibiotics, which further exacerbate intestinal dysbiosis and leave the patient acutely sensitive to reinfection. Development of novel targeted therapeutic interventions will require a detailed knowledge of essential cellular processes, which represent attractive targets, and species-specific processes, such as bacterial sporulation. Our knowledge of the genetic basis of C. difficile infection has been hampered by a lack of genetic tools, although recent developments have made some headway in addressing this limitation. Here we describe the development of a method for rapidly generating large numbers of transposon mutants in clinically important strains of C. difficile. We validated our transposon mutagenesis approach in a model strain of C. difficile and then generated a comprehensive transposon library in the highly virulent epidemic strain R20291 (027/BI/NAP1) containing more than 70,000 unique mutants. Using transposon-directed insertion site sequencing (TraDIS), we have identified a core set of 404 essential genes, required for growth in vitro. We then applied this technique to the process of sporulation, an absolute requirement for C. difficile transmission and pathogenesis, identifying 798 genes that are likely to impact spore production. The data generated in this study will form a valuable resource for the community and inform future research on this important human pathogen.},
  language  = {en}
}
@article{OkoroBarquistConnoretal.2015,
  author    = {Okoro, Chinyere K. and Barquist, Lars and Connor, Thomas R. and Harris, Simon R. and Clare, Simon and Stevens, Mark P. and Arends, Mark J. and Hale, Christine and Kane, Leanne and Pickard, Derek J. and Hill, Jennifer and Harcourt, Katherine and Parkhill, Julian and Dougan, Gordon and Kingsley, Robert A.},
  title     = {Signatures of adaptation in human invasive Salmonella Typhimurium ST313 populations from sub-Saharan Africa},
  series = {PLoS Neglected Tropical Diseases},
  volume    = {9},
  journal   = {PLoS Neglected Tropical Diseases},
  number    = {3},
  doi       = {10.1371/journal.pntd.0003611},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143779},
  pages     = {e0003611},
  year      = {2015},
  abstract  = {Two lineages of Salmonella enterica serovar Typhimurium (S. Typhimurium) of multi-locus sequence type ST313 have been linked with the emergence of invasive Salmonella disease across sub-Saharan Africa. The expansion of these lineages has a temporal association with the HIV pandemic and antibiotic usage. We analysed the whole genome sequence of 129 ST313 isolates representative of the two lineages and found evidence of lineage-specific genome degradation, with some similarities to that observed in S. Typhi. Individual ST313 S. Typhimurium isolates exhibit a distinct metabolic signature and modified enteropathogenesis in both a murine and cattle model of colitis, compared to S. Typhimurium outside of the ST313 lineages. These data define phenotypes that distinguish ST313 isolates from other S. Typhimurium and may represent adaptation to a distinct pathogenesis and lifestyle linked to an-immuno-compromised human population.},
  language  = {en}
}