Dr Andrew Preston
Profile
Research in the group is in the broad area of bacterial pathogenesis. In particular our work is focused on the genus Bordetella. This group includes important pathogens of humans and animal, notably the main causative agent of Whooping Cough, B. pertussis. It also includes non-pathogenic, environmental species and some species for which the reservoirs are unclear and their true pathogenic nature is unknown.
Our studies encompass fundmental investigations of bacterial factors important to the infection biology of these bacteria, with an emphasis on surface polysaccharides such as lipopolysaccharide (LPS); more applied projects such as defining Bordetella metabolism with the aim of improving in vitro culture processes for vaccine production and elucidation of the evolutionary relationships between these and other bacteria.
Infection Biology
We have defined structure function relationships for many of the different regions of Bordetella LPS, including the role of the Band A trisaccharide and O polysaccharide in infection and immunity. We continue to investigate the genetic basis for LPS biosynthesis among the Bordetella and use this information to make defined genetic mutants whose phenotypes reveal the role of particular structures in infection.
Collaborators: Dr Eric Harvill, Penn State University, USA; Dr Bob Ernst, University of Baltimore-Maryland, USA.
Metabolism
We are generating genome-scale metabolic models for B. pertussis metabolism with the aim of improving on current culture methods for use in biotechnology and vaccine production. This work combines mathematical modeling with wet lab studies, in cycles of model validation and refinement.
Collaborators: Dr Caroline Colijn, Imperial College, London; Dr Philippe Dehottay & Dr Philippe Goffin, GSK Biologicals, Rixensaart, Belgium.
Evolution
We have a long standing involvement of generating and analysing genome sequences for the bordetellae. We are currently involved in a large scale analysis of the global population structure of B. pertussis, focused analysis of current UK B. pertussis strains and evolutionary relationships between all members of the genus.
Collaborators: Simon Harris & Julian Parkhill, Sanger Institute, Hinxton, UK; Dr Eric Harvill, Penn State University, USA.
Publications
Hauser, H., Richter, D. C., van Tonder, A., Clark, L. and Preston, A., 2012. Comparative genomic analyses of the Taylorellae. Veterinary Microbiology, 159 (1-2), pp. 195-203.
MacArthur, I., Jones, J. W., Goodlett, D. R., Ernst, R. K. and Preston, A., 2011. Role of pagL and lpxO in Bordetella bronchiseptica lipid A biosynthesis. Journal of Bacteriology, 193 (18), pp. 4726-4735.
Loker, S. B., Temple, L. M. and Preston, A., 2011. The Bordetella avium BAV1965-1962 fimbrial locus is regulated by temperature and produces fimbriae involved in adherence to turkey tracheal tissue. Infection and Immunity, 79 (6), pp. 2423-2429.
Kubler-Kielb, J., Vinogradov, E., Lagergård, T., Ginzberg, A., King, J. D., Preston, A., Maskell, D. J., Pozsgay, V., Keith, J. M., Robbins, J. B. and Schneerson, R., 2011. Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica induce bactericidal antibodies, an addition to pertussis vaccine. Proceedings of the National Academy of Sciences of the United States of America, 108 (10), pp. 4087-4092.
Vinogradov, E., King, J. D., Pathak, A. K., Harvill, E. T. and Preston, A., 2010. Antigenic variation among Bordetella: Bordetella bronchiseptica strain MO149 expresses a novel o chain that is poorly immunogenic. Journal of Biological Chemistry, 285 (35), pp. 26869-26877.
King, J. D., Vinogradov, E., Preston, A., Li, J. and Maskell, D. J., 2009. Post-assembly modification of Bordetella bronchiseptica O polysaccharide by a novel periplasmic enzyme encoded by wbmE. Journal of Biological Chemistry, 284 (3), pp. 1474-1483.
Rejzek, M., Sri Kannathasan, V., Wing, C., Preston, A., Westman, E. L., Lam, J. S., Naismith, J. H., Maskell, D. J. and Field, R. A., 2009. Chemical synthesis of UDP-Glc-2,3-diNAcA, a key intermediate in cell surface polysaccharide biosynthesis in the human respiratory pathogens B. pertussis and P. aeruginosa. Organic & Biomolecular Chemistry, 7 (6), pp. 1203-1210.
Buboltz, A. M., Nicholson, T. L., Karanikas, A. T., Preston, A. and Harvill, E. T., 2009. Evidence for horizontal gene transfer of two antigenically distinct O antigens in Bordetella bronchiseptica. Infection and Immunity, 77 (8), pp. 3249-3257.
Zhang, X., Goebel, E. M., Rodríguez, M. E., Preston, A. and Harvill, E. T., 2009. The O antigen is a critical antigen for the development of a protective immune response to Bordetella parapertussis. Infection and Immunity, 77 (11), pp. 5050-5058.
Westman, E. L., Preston, A., Field, R. A. and Lam, J. S., 2008. Biosynthesis of a rare di-N-acetylated sugar in the lipopolysaccharides of both Pseudomonas aeruginosa and Bordetella pertussis occurs via an identical scheme despite different gene clusters. Journal of Bacteriology, 190 (18), pp. 6060-6069.
