Wren Lab, Clostridium difficile
Genetic basis of Clostridium difficile
Principal investigator: Brendan Wren
Co-Investigators: Richard Stabler, Lisa Dawson, Esmeralda Valiente, Melissa Martin, Elizabeth Donahue, Michelle Cairns, Fatima Al-Khattaf, Alex Faulds-Pain.
Funder: Wellcome Trust and MRC
Objectives: The objectives of the project are to determine the genetic basis of Clostridium difficile infection. Specific aims are to:
- exploit genome sequence to identify novel virulance determinants
- use comparative genome analysis to correlate virulence with gene content
- use whole genome analysis to study the emergence of hypervirulent strains
- ascertain the importance of p-cresol production
- develop phenotype assays to study genome to phenome
- the role of glycosylation in C. difficile
- the role of sortase and sorted proteins
Output from the project:
- Dawson, L.F.; Donahue, E.H.; Cartman, S.T.; Barton, R.H.; Bundy, J.; McNerney, R.; Minton, N.P.; Wren, B.W. The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains. BMC Microbiol (2011) Apr 28; 11(1):86
- Valiente, E.; Dawson, L.F.; Cairns, M.D.; Stabler, R.A.; Wren, B.W. Emergence of new PCR-ibotypes from the hypervirulent Clostridium difficile 027 lineage. J Med Microbiol. (2011) Sep 8
- Dawson, L.F.; Valiente, E.; Donahe, E.H.; Birchenough, G.; Wren, B.W. Hypervirulent Clostridium difficile PCR-ribotypes exhibit resistance to widely used disinfectants. PLoS One. 2011;6(10):e25754. Epub 2011 Oct 25
- Stabler, R.A.; Valiente, E.; Dawson, L.F.; He, M.; Parkhill, J.; Wren, B.W. In-depth genetic analysis of Clostridium difficile PCr-ribotype 027 strains reveal high genome fluidity including point mutations and inversions. Gut Microbes. (2010) 1(4):269-276
- He, M.; Sebaihia, M.; Lawley, T.D.; Stabler, R.A.; Dawson, L.F.; Martin, M.J.; Holt, K.E.; Seth-Smith, H.M.; Quail, M.A.; Rance, R.; Brooks, K.; Churcher, C.; Harris, D.; Bentley, S.D.; Burrows, C.; Clark, L.; Corton, C.; Murray, V.; Rose, G.; Thurston, S.; van Tonder, A.; Walker, D.; Wren, B.W.; Dougan, G.; Parkhill, J. (2010) Evolutionary dynamics of Clostridium difficile over short and long time scales. Proc Natl Acad Sci U S A, 107(16):7527-32
- Stabler, R.A.; He, M.; Dawson, L.; Martin, M.; Valiente, E.; Corton, C.; Lawley, T.D.; Sebaihia, M.; Quail, M.A.; Rose, G.; Gerding, D.N.; Gibert, M.; Popoff, M.R.; Parkhill, J.; Dougan, G.; Wren, B.W. (2009) Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium. Genome Biol 10(9):R102
- Lawley, T.D.; Clare, S.; Walker, A.W.; Goulding, D.; Stabler, R.A.; Croucher, N.; Mastroeni, P.; Scott, P.; Raisen, C.; Mottram, L.; Fairweather, N.F.; Wren, B.W.; Parkhill, J.; Dougan, G. (2009) Antibiotic treatment of Clostridium difficile carrier mice triggers a supershedder state, spore-mediated transmission, and severe disease in immunocompromised hosts. Infect Immun, 77(9):3661-9
- Dawson, L.F.; Valiente, E.; Wren, B.W. (2009) Clostridium difficile - a continually evolving and problematic pathogen. Infect Genet Evol, 9(6):1410-7
- Dawson, L.F.; Stabler, R.A.; Wren, B.W.(2008) Assessing the role of p-cresol tolerance in Clostridium difficile. J Med Microbiol, 57(Pt 6):745-9
- Stabler, R.A., Gerding, D.N., Songer, J.G., Drudy, D., Brazier, J.S., Trinh, H.T., Witney, A.A., Hinds, J., Wren, B.W. (2006) Comparative phylogenomics of Clostridium difficile reveals clade specificity and microevolution of hypervirulent strains. J Bacteriol, 188(20):7297-7305
- Wren, B.W. (2006) Clostridium difficile comes of age. Future Medicine, 1:243-245
- Sebaihia M, Wren BW, Mullany P, Fairweather NF, Minton N, Stabler R, Thomson NR, Roberts AP, Cerdeno-Tarraga AM, Wang H, Holden MT, Wright A, Churcher C, Quail MA, Baker S, Bason N, Brooks K, Chillingworth T, Cronin A, Davis P, Dowd L, Fraser A, Feltwell T, Hance Z, Holroyd S, Jagels K, Moule S, Mungall K, Price C, Rabbinowitsch E, Sharp S, Simmonds M, Stevens K, Unwin L, Whithead S, Dupuy B, Dougan G, Barrell B, Parkhill J (2006) The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome. Nature Genetics, Jul 38(7): 779-786
- Ward, S.J., Douce, G., Dougan, G. & Wren, B.W. (1999a). Local and systemic neutralizing antibody responses induced by intranasal immunization with the nontoxic binding domain of toxin A from Clostridium difficile. Infect Immun 67(10): 5124-32
- Ward, S.J., Douce, G., Figueiredo, D., Dougan, G. & Wren, B.W. (1999b). Immunogenicity of a Salmonella typhimurium aroA aroD vaccine expressing a nontoxic domain of Clostridium difficile toxin A. Infect Immun 67(5): 2145-52
- Calabi, E., Ward, S., Wren, B.W., Paxton, T., Panico, M., Morris, H., Dell, A., Dougan, G. & Fairweather, N. (2001). Molecular characterization of the surface layer proteins from Clostridium difficile. Mol Microbiol 40(5): 1187-99
