My interest in microbiology began as an undergraduate at the University of Newcastle-on-Tyne (UK). I had planned to pursue a degree in another discipline and took a first-year course in microbiology, largely to see what it was all about. I became fascinated by bacterial systems and their contributions to our understanding of many of the critical fundamental questions in biology. I ended up switching my major and developed an interest that still drives my research and teaching today. I was first introduced to the area of prokaryotic glycobiology in my Ph.D. work at the University of Edinburgh, and expanded my knowledge of this broad field through postdoctoral fellowships at the University of California at Davis and the University of Calgary. Since joining the University of Guelph, my research group’s focus has been on the structure and assembly of bacterial cell surfaces. This has its roots in those postdoctoral studies but now involves a variety of different membrane trafficking systems. With the ever-advancing sophistication of experimental methods we are now able to address key scientific questions at an unprecedented level of molecular detail. There are always further important questions to ask and our interest and continued progress are now enhanced by the integration of multidisciplinary approaches, and valued international collaborations.
Research in my laboratory is focused on the architecture and assembly of the cell surfaces of pathogenic bacteria. Complex molecular machines coordinate the synthesis and export of cell-surface macromolecules and our goal is to understand their structure and function. This represents a fascinating challenge for experimental research and involves the application of a range of experimental strategies that span the disciplines of biochemistry, microbiology, molecular biology, and structural biology. The systems being investigated are of fundamental importance in understanding the physiology and pathogenesis of bacteria and they may yield new therapeutic strategies for intervention in bacterial infections.
Current areas of emphasis are:
Structure and function of multi-enzyme complexes required for the export of capsular polysaccharides through the periplasm and across the outer membrane of Gram-negative bacteria.
Structural basis for substrate recognition by ABC transporters involved in the export of bacterial cell-surface polysaccharides.
Structure and function studies of prokaryotic glycosyltransferase enzymes.
Mechanisms that couple glycan biosynthesis and chain extension to transport pathways.
Bi, Y., E. Mann, C. Whitfield, and J. Zimmer. 2018. Architecture of a channel-forming O-antigen polysaccharide ABC transporter. Nature. 553: 361-365.
Stokes, J.M., C.R. MacNair, B. Ilyas, S. French, J.-P. Côté, C. Bouwman, M.A. Farha, A.O. Sieron, C. Whitfield, B.K. Coombes, and E.D. Brown. 2017. An antiprotozoal drug overcomes acquired colistin resistance. Nature Microbiology 2: 17028.
Williams, D.M., O.G. Ovchinnikova, A. Koizumi, I.L. Mainprize, M.S. Kimber, T.L. Lowary, and C. Whitfield. 2017. A single polysaccharide assembly protein that integrates polymerization, termination and chain-length quality control. Proceedings of the National Academy of Sciences USA 114: E121-E1223.
Ovchinnikova, O.G., L. Doyle, B-S. Huang M.S. Kimber, T.L. Lowary, and C. Whitfield. 2016. Biochemical characterization of bifunctional 3-deoxy-β-D-manno-oct-2-ulosonic acid (β‑Kdo) transferase KpsC from Escherichia coli involved in capsule biosynthesis. Journal of Biological Chemistry 291: 21519-21530.
Liston, S.D., O.G. Ovchinnikova, and C. Whitfield. 2016. A unique lipid anchor attaches Vi antigen capsule to the surface of Salmonella enterica serovar Typhi. Proceedings of the National Academy of SciencesUSA 113: 6719-6724.
Ovchinnikova, O.G., E. Mallette, A. Koizumi, T.L. Lowary, M.S. Kimber, and C. Whitfield. 2016. Bacterial ß-Kdo glycosyltransferases represent a new glycosyltransferase family (GT99). Proceedings of the National Academy of Sciences USA 113: E3120-E3129.
Mann, E., E. Mallette, B.R. Clarke, M.S. Kimber, and C. Whitfield. 2016. The Klebsiella pneumoniae O12 ATP-binding cassette (ABC) transporter recognizes the terminal residue of its O-antigen polysaccharide substrate. Journal of Biological Chemistry. 291: 9748-9761.
Stokes, J.M., French S., Ovchinnikova, O.G., Bouwman, C., Whitfield, C., and Brown, E.D. 2016. Cold stress makes Escherichia coli susceptible to glycopeptide antibiotics by altering outer membrane integrity. Cell Chemical Biology 23: 267-277.
Mann, E., O.G. Ovchinnikova, J.D. King, and C. Whitfield. 2015. Bacteriophage-mediated glucosylation can modify lipopolysaccharide O antigens synthesized by an ABC transporter-dependent assembly mechanism. Journal of Biological Chemistry. 290: 26661-25570.
Liston, S.D., B.R. Clarke, L.K. Greenfield, M.R. Richards, T.L. Lowary, and C. Whitfield. 2015. Domain interactions control complex formation and polymerase specificity in the biosynthesis of the Escherichia coli O9a antigen. Journal of Biological Chemistry: 290: 1075-1085.
Hagelueken, G., B.R. Clarke, H. Huang, A. Tuukanen, I. Danciu, D.I. Severgun, H. Liu, C. Whitfield and J.H. Nasimith. 2015. A coiled-coil structural domain acts as a molecular ruler in chain length regulation of the Escherichia coli O9a antigen. Nature Structural and Molecular Biology. 22: 50-56.
Nickerson, N.N., I.L. Mainprize, L. Hampton, M.L. Jones, J.H. Naismith, and C. Whitfield. 2014. Trapped translocation intermediates establish the route for export of capsular polysaccharides across Escherichia coli outer membranes. Proceedings of the National Academy of Sciences USA 111: 8203-8208
King, J.D., S. Berry, B.R. Clarke, R.J. Morris and C. Whitfield. 2014. Lipopolysaccharide O antigen size distribution is determined by a chain extension complex of variable stoichiometry in Escherichia coli O9a.Proceedings of the National Academy of Sciences USA 111: 6407-6412.
Willis, L.M., and C. Whitfield. 2013. KpsC and KpsS are retaining 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferases involved in synthesis of bacterial capsules. Proceedings of the National Academy of Sciences USA 110: 20753-20758.
Willis, L.M., J. Stupak, M.R. Richards, T.L. Lowary, J. Li, and C. Whitfield. 2013. Conserved glycolipid termini in capsular polysaccharides synthesized by ATP-binding cassette transporter-dependent pathways in Gram-negative pathogens. Proceedings of the National Academy of Sciences USA 110: 7868-7873.