Wren Lab, Yersinia
Genetic and molecular characterisation of pathogenic Yersinia
Principal investigator: Brendan Wren
Co-Investigators: George Joshua, Dominic Mills
Funder: DSTL and the BBSRC
Objectives: The objectives of the project are to determine the genetic basis by which pathogenic Yersinia causedisease. Specific aims are to:
- study the molecular evolution of virulence of pathogenic Yersinia
- decipher the PhoP/PhoQ regulatory pathway
- develop the C. elegans/Yersinia biofilm infection as a surrogate infection model
- quorum sensing and lifestyle adaptations
Output from the project:
- Oyston, P.C., Dorrell, N., Williams, K., Li, S.R., Green, M., Titball, R.W. & Wren, B.W. (2000). The response regulator PhoP is important for survival under conditions of macrophage-induced stress and virulence in Yersinia pestis. Infect Immun 68: 3419-25
- Wren, B.W. (2000). Microbial genome analysis: insights into virulence, host adaptation and evolution. Nat Rev Genet 1: 30-9
- Prentice, M.B., James, K.D., Parkhill, J., Baker, S.G., Stevens, K., Simmonds, M.N., Mungall, K.L., Churcher, C., Oyston, P.C., Titball, R.W., Wren, B.W., Wain, J., Pickard, D., Hien, T.T., Farrar, J.J. & Dougan, G. (2001). Yersinia pestis pFra shows biovar-specific differences and recent common ancestry with a Salmonella enterica serovar Typhi plasmid. Journal of Bacteriology 183: 2586-94
- Prior, J.L., Parkhill, J., Hitchen, P.G., Mungall, K.L., Stevens, K., Morris, H.R., Reason, A.J., Oyston, P.C., Dell, A., Wren, B.W. & Titball, R.W. (2001a). The failure of different strains of Yersinia pestis to produce lipopolysaccharide O-antigen under different growth conditions is due to mutations in the O-antigen gene cluster. FEMS Microbiol Lett 197: 229-33
- Prior, J.L., Hitchen, P.G., Williamson, D.E., Reason, A.J., Morris, H.R., Dell, A., Wren, B.W. & Titball, R.W. (2001b). Characterization of the lipopolysaccharide of Yersinia pestis. Microbial Pathogenesis 30: 49-57
- Karlyshev, A.V., Oyston, P.C., Williams, K., Clark, G.C., Titball, R.W., Winzeler, E.A. & Wren, B.W. (2001). Application of high-density array-based signature-tagged mutagenesis to discover novel Yersinia virulence-associated genes. Infect Immun 69: 7810-9
- Parkhill, J., Wren, B.W., Thomson, N.R., Titball, R.W., Holden, M.T., Prentice, M.B., Sebaihia, M., James, K.D., Churcher, C., Mungall, K.L., Baker, S., Basham, D., Bentley, S.D., Brooks, K., Cerdeno-Tarraga, A.M., Chillingworth, T., Cronin, A., Davies, R.M., Davis, P., Dougan, G., Feltwell, T., Hamlin, N., Holroyd, S., Jagels, K., Karlyshev, A.V., Leather, S., Moule, S., Oyston, P.C., Quail, M., Rutherford, K., Simmonds, M., Skelton, J., Stevens, K., Whitehead, S. & Barrell, B.G. (2001). Genome sequence of Yersinia pestis, the causative agent of plague. Nature 413: 523-7
- Hinchcliffe, S.J., Isherwood, K.E., Stabler, R.A., Oyston, P.C.F., Hinds, J., Titball, R.W. & Wren, B.W. (2002). Separated at birth? Microarray analysis of two strikingly similar Yersinia species. Comparative and Functional Genomics 3: 355-357
- Hitchen, P.G., Prior, J.L., Oyston, P.C., Panico, M., Wren, B.W., Titball, R.W., Morris, H.R. & Dell, A. (2002). Structural characterization of lipo-oligosaccharide (LOS) from Yersinia pestis: regulation of LOS structure by the PhoPQ system. Mol Microbiol 44: 1637-50
- Joshua, G.W., Karlyshev, A.V., Smith, M.P., Isherwood, K.E., Titball, R.W. & Wren, B.W. (2003). A Caenorhabditis elegans model of Yersinia infection: biofilm formation on a biotic surface. Microbiology 149: 3221-9
- Hinchliffe, S.J., Isherwood, K.E., Stabler, R.A., Prentice, M.B., Rakin, A., Nichols, R.A., Oyston, P.C., Hinds, J., Titball, R.W. & Wren, B.W. (2003). Application of DNA Microarrays to Study the Evolutionary Genomics of Yersinia pestis and Yersinia pseudotuberculosis. Genome Res 13: 2018-29
- Wren, B.W. (2003). The yersiniae--a model genus to study the rapid evolution of bacterial pathogens. Nat Rev Microbiol 1: 55-64
- Waterfield N.R., Wren B.W. & Ffrench-Constant R.H. (2004) Invertebrates as a source of emerging human pathogens. Nat Rev Microbiol 2(10):833-841
- Erickson DL, Jarrett Co, Wren BW, Hinnebusch BJ (2006) Serotype differences and lack of biofilm formation characterize Yersinia pseudotuberculosis infection of the Xenopsylla cheopis flea vector of Yersinia pestis. J Bacteriology 188:1113-1119
- Howard S, Gaunt M, Hinds J, Witney A, Stabler R, Wren BW (2006) Application of comparative phylogenomics to study the evolution of Yersinia enterocolitica and to identify genetic differences relating to virulence. J Bacteriology 188:3645-3653
- 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):7297-305
- Cathelyn, J.S.; Ellison, D.W.; Hinchliffe, S.J.; Wren, B.W.; Miller, V.L. 2007 The RovA regulons of Yersinia enterocolitica and Yersinia pestis are distinct: evidence that many RovA-regulated genes were acquired more recently than the core genome. Mol Microbiol 66(1):189-205
- Thomson, N.R.; Howard, S.; Wren, B.W.; Prentice, M.B. 2007 Comparative genome analyses of the pathogenic Yersiniae based on the genome sequence of Yersinia enterocolitica strain 8081. Adv Exp Med Biol 603:2-16
- Hinchliffe, S.J.; Howard, S.L.; Huang, Y.H.; Clarke, D.J.; Wren, B.W. 2008 The importance of the Rcs phosphorelay in the survival and pathogenesis of the enteropathogenic yersiniae. Microbiology 154(Pt 4):1117-31
- Champion, O.L.; Cooper, I.A.M.; James, S.L.; Ford, D.; Karlyshev, A.; Wren, B.W.; Duffield, M.; Oyston, P.C.F.; Titball, R.W. 2009 Galleria mellonella as an alternative infection model for Yersinia pseudotuberculosis. Microbiology-Sgm 155:1516-1522
- Axler-Diperte, G.L.; Hinchliffe, S.J.; Wren, B.W.; Darwin, A.J. 2008 YtxR acts as an overriding transcriptional off switch for the Yersinia enterocolitica Ysc-Yop type 3 secretion system. J Bacteriol 191(2):514-24
- Champion, O.L.; Karlyshev, A.V.; Cooper, I.A.; Ford, D.C.; Wren, B.W.; Duffield, M.L.; Oyston, P.C.; Titball, R.W. Yersinia pseudotuberculosis mntH functions in intracellular manganese accumulation that is essential for virulence and survival in cells expressing functional Nramp1. Microbiology. (2010) 156:2666-2670
- Strong, P.C.; Hinchliffe, S.J.; Patrick, H.; Atkinson, S.; Champion, O.L.; Wren, B.W. Identification and characterisation of a novel adhesin Ifp in Yersinia pseudotuberculosis. BMC Microbiol. (2011) Apr 28;11(1)85
- Atkinson, S.; Goldstone, R.J.; Joshua, G.W.; Chang, C.Y.; Patrick, H.L.; Camara, M.; Wren, B.W.; Williams, P. Biofilm development on Caenorhabditis elegans by Yersinia is facilitated by quorum sensing-dependent repression of type III secretion. PLoS Pathog. (2011);7(1):e1001250
