Wren Lab, Campylobacter jejuni
Genetic and molecular characterisation of the gastrointestinal pathogen Campylobacter jejuni
Principal investigator: Brendan Wren
Co-Investigators: Nick Dorrell, Richard Stabler Abdi Elmi, Ozan Gundogdu
Funder: BBSRC
Objectives:
- The objectives of the project are to determine the genetic basis by which C. jejuni causes gastrointestinal disease and neurological complications. Specific aims are to:
- Determine the role of the capsule in the survival and virulence of C. jejuni
- Ascertain the importance of biofilm formation
- Identify correlates of pathogenicity through whole genome microarray analysis
- Decipher and exploit Campylobacter glycosylation systems for glyco-engineering
Output from the project:
- Parkhill, J., Wren, B.W., Mungall, K., Ketley, J.M., Churcher, C., Basham, D., Chillingworth, T., Davies, R.M., Feltwell, T., Holroyd, S., Jagels, K., Karlyshev, A.V., Moule, S., Pallen, M.J., Penn, C.W., Quail, M.A., Rajandream, M.A., Rutherford, K.M., van Vliet, A.H., Whitehead, S. & Barrell, B.G. (2000). The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 403: 665-8
- Karlyshev, A.V., Linton, D., Gregson, N.A., Lastovica, A.J. & Wren, B.W. (2000). Genetic and biochemical evidence of a Campylobacter jejuni capsular polysaccharide that accounts for Penner serotype specificity. Mol Microbiol 35: 529-41
- Linton, D., Karlyshev, A.V., Hitchen, P.G., Morris, H.R., Dell, A., Gregson, N.A. & Wren, B.W. (2000). Multiple N-acetyl neuraminic acid synthetase (neuB) genes in Campylobacter jejuni: identification and characterization of the gene involved in sialylation of lipo-oligosaccharide. Mol Microbiol 35: 1120-34
- Wren, B.W. (2000). Microbial genome analysis: insights into virulence, host adaptation and evolution. Nat Rev Genet 1: 30-9
- Karlyshev, A.V., McCrossan, M.V. & Wren, B.W. (2001b). Demonstration of polysaccharide capsule in Campylobacter jejuni using electron microscopy. Infect Immun 69: 5921-4
- Dorrell, N., Mangan, J.A., Laing, K.G., Hinds, J., Linton, D., Al-Ghusein, H., Barrell, B.G., Parkhill, J., Stoker, N.G., Karlyshev, A.V., Butcher, P.D. & Wren, B.W. (2001). Whole genome comparison of Campylobacter jejuni human isolates using a low-cost microarray reveals extensive genetic diversity. Genome Res 11: 1706-15
- Linton, D., Allan, E., Karlyshev, A.V., Cronshaw, A.D. & Wren, B.W. (2002). Identification of N-acetylgalactosamine-containing glycoproteins PEB3 and CgpA in Campylobacter jejuni. Mol Microbiol 43: 497-508
- Wacker, M., Linton, D., Hitchen, P.G., Nita-Lazar, M., Haslam, S.M., North, S.J., Panico, M., Morris, H.R., Dell, A., Wren, B.W. & Aebi, M. (2002). N-linked glycosylation in Campylobacter jejuni and its functional transfer into E. coli. Science 298: 1790-3
- Szymanski, C.M., Logan, S.M., Linton, D. & Wren, B.W. (2003). Campylobacter--a tale of two protein glycosylation systems. Trends in microbiology 11: 233-8
- Zilbauer M, Dorrell N, Boughan PK, Harris, A, Wren BW, Klein NJ, Bajaj-Elliott M. (2005) Intestinal innate immunity to Campylobacter jejuni results in induction of bactericidal human beta-defensins 2 and 3. Infection and Immunity 73:7281-7289
- Karlyshev AV, Champion OL, Churcher C, Brisson JR, Jarrell HC, Gilbert M, Brochu D, St Michael F, Li J, Wakarchuk WW, Goodhead I, Sanders M, Stevens K, White B, Parkhill J, Wren BW, Szymanski CM. (2005) Analysis of Campylobacter jejuni capsular loci reveals multiple mechanisms for the generation of structural diversity and the ability to form complex heptoses. Molecular Microbiology 55:90-103
- Linton D, Dorrell N, Hitchen PG, Amber S, Karlyshev AV, Morris HR, Dell A, Valvano MA, Aebi M, Wren BW (2005) Functional analysis of the Campylobacter jejuni N-linked protein glycosylation pathway. Molecular Microbiology 55:1695-1703
- Szymanski CM, Wren BW (2005) Protein glycosylation in bacterial mucosal pathogens. Nature Reviews Microbiology 3:225-237
- Champion OL, Gaunt MW, Gundogdu O, Elmi A, Witney AA, Hinds J, Dorrell N, Wren BW (2005) Comparative phylogenomics of the food-borne pathogen Campylobacter jejuni reveals genetic markers predictive of infection source. Proc Natl Acad Sci USA 102:16043-16048
- Joshua GW, Guthrie-Irons C, Karlyshev AV, Wren BW (2006) Biofilm formation in Campylobacter jejuni. Microbiology 152:387-396
- Gundogdu O, Bentley SD, Hodlen MT, Parkhill J, Dorrell N, Wren BW (2007) Re-annotation and re-analysis of the Campylobacter jejuni NCTC11168 genome sequence. BMC Genomics 8:162
- Kamal N, Dorrell N, Jagannathan A, Turner SM, Constantinidou C, Studholme DJ, Marsden G, Hinds J, Laing KG, Wren BW, Penn CW (2007) Deletion of a previously uncharacterized flagellar-hook-length control gene fliK modulates the sigma54-dependent regulon in Campylobacter jejuni. Microbiology, 153(Pt 9):3099-3111
- McNally DJ, Lamoureux MP, Karlyshev AV, Fiori LM, Li J, Thacker G, Coleman RA, Khieu NH, Wren BW, Brisson JR, Jarrell HC, Szymanski CM (2007) Commonality and biosynthesis of the O-methyl phosphoramidate capsule modification in Campylobacter jejuni. J Biol Chem 282(39):28566-28576
- Zilbauer M, Dorrell N, Elmi A, Lindley KJ, Schuller S, Jones HE, Klein NJ, Nunez G, Wren BW, Bajaj-Elliott M (2007) A major role for intestinal epithelial nucleotide oligomerization domain 1 (NOD1) in eliciting host bactericidal immune responses to Campylobacter jejuni. Cell Microbiol 9(10):2404-2416
- Howard SL, Jagannathan A, Soo EC, Hui JP, Aubry AJ, Ahmed I, Karlyshev A, Kelly JF, Jones MA, Stevens MP, Logan SM, Wren BW (2009) A Campylobacter jejuni glycosylation island important in cell charge, legionaminic acid biosynthesis and colonisation of chickens. Infect Immun 77(6):2544-56
- Champion OL, Karlyshev AV, Senior NJ, Woodward M, La Ragione R, Howard SL, Wren BW, Titball RW (2010) Insect Infection Model for Campylobacter jejuni Reveals That O-methyl Phosphoramidate Has Insecticidal Activity. J Infect Dis 201(5):776-82.
- Edwards, L.A.; Nistala, K.; Mills, D.C.; Stephenson, H.N.; Zilbauer, M.; Wren, B.W., Dorrell, N.; Lindley, K.J.; Wedderburn, L.R.; Bajaj-Elliott, M. Delineation of the Innate and Adaptive T-Cell Immune Outcome in the Human Host in Response to Campylobacter jejuni Infection. PLoS One. (2010) 5(11):e15398
- Champion, O.L.; Karlyshev, A.V.; Senior, N.J.; Woodward, M.; La Ragione, R.; Howard, S.L.; Wren, B.W.; Titball, R.W. Insect infection model for Campylobacter jejuni reveals that O-methyl phosphoramidate has insecticidal activity. J Infect Dis. (2010); 201(5):776-82
- Rose, A.; Kay, E.; Wren, B.W.; Dallman, M.J. The Campylobacter jejuni NCTC11168 capsule prevents excessive cytokine production by dendritic cells. Med Microbiol Immunol. 2011 Aug 24
- Gundogdu, O.; Mills, D.C.; Elmi, A.; Martin, M.J.; Wren, B.W.; Dorrell, N. The Campylobacter jejuni transcriptional regulator Cjl556 plays a role in oxidative and aerobic stress response and is important for bacterial survival in vitro. J Bacteriol. (2011) Aug;193(16):4238-49
