TY  - JOUR
A1  - Okoro, Chinyere K.
A1  - Barquist, Lars
A1  - Connor, Thomas R.
A1  - Harris, Simon R.
A1  - Clare, Simon
A1  - Stevens, Mark P.
A1  - Arends, Mark J.
A1  - Hale, Christine
A1  - Kane, Leanne
A1  - Pickard, Derek J.
A1  - Hill, Jennifer
A1  - Harcourt, Katherine
A1  - Parkhill, Julian
A1  - Dougan, Gordon
A1  - Kingsley, Robert A.
T1  - Signatures of adaptation in human invasive Salmonella Typhimurium ST313 populations from sub-Saharan Africa
JF  - PLoS Neglected Tropical Diseases
N2  - 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.
KW  - genome sequence
KW  - infection
KW  - pathogenicity
KW  - children
KW  - disease
KW  - adults
KW  - identification
KW  - Escherichia coli
KW  - virulence
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143779
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Dembek, Marcin
A1  - Barquist, Lars
A1  - Boinett, Christine J.
A1  - Cain, Amy K.
A1  - Mayho, Matthew
A1  - Lawley, Trevor D.
A1  - Fairweather, Neil F.
A1  - Fagan, Robert P.
T1  - High-throughput analysis of gene essentiality and sporulation in Clostridium difficile
JF  - mBio
N2  - 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.
KW  - Bacillus subtilis
KW  - expression
KW  - spores
KW  - toxin
KW  - transcription
KW  - germination
KW  - transposition
KW  - metabolism
KW  - infection
KW  - in vitro
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143745
VL  - 6
IS  - 2
ER  -