Genetic
and molecular characterisation of the gastrointestinal pathogen Campylobacter
jejuni
- Principal investigator: Brendan
Wren
- Co-Investigators: Nick Dorrell, Gillian Thacker,
Rebecca Langdon, Suadd Al-Jaberi, Collette Guthrie, Emily Kay, 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 contingency genes in phase variation of C.
jejuni
Resolve the importance of glycosylation in host adaptation
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
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Output from the project:
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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
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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
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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
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Wren, B.W. (2000). Microbial
genome analysis: insights into virulence, host adaptation and evolution.
Nat Rev Genet 1: 30-9
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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
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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
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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
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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
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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
- 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
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