Dr. Chris Whitfield

Dr. Chris Whitfield
Professor
Department of Molecular and Cellular Biology
Email: 
cwhitfie@uoguelph.ca
Phone number: 
53361 / 54710
Office: 
SSC 4245
Lab: 
SSC 4202

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.

Dr. Whitfield is no longer taking graduate students.

  • B.Sc. University of Newcastle-upon-Tyne
  • Ph.D. University of Edinburgh

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:

  1. 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.
  2. Structural basis for substrate recognition by ABC transporters involved in the export of bacterial cell-surface polysaccharides.
  3. Structure and function studies of prokaryotic glycosyltransferase enzymes.
  4. Mechanisms that couple glycan biosynthesis and chain extension to transport pathways.

Kelly, S.D., M.J. Allas, L.D. Goodrich, T.L. Lowary and C. Whitfield. 2024. Structure, biosynthesis and regulation of the T1 antigen, a phase-variable surface polysaccharide conserved in many Salmonella serovars. Nature Communications 15: 5604 https://www.nature.com/articles/s41467-024-50957-y

Kelly, S.D., D.M. Williams, S. Zhu, T. Kim, M. Jana, J. Nothof, V. Narasimharao Thota, T.L. Lowary, and C. Whitfield. 2024. Klebsiella pneumoniae O-polysaccharide biosynthesis highlights the diverse organization of catalytic modules in ABC transporter-dependent glycan assembly. Journal of Biological Chemistry 300: 107420 https://www.jbc.org/article/S0021-9258(24)01921-5/fulltext

Litschko, C., V. Di Domenico, J. Schulze, S. Li, O.G. Ovchinnikova, T. Voskuilen, A. Bethe, J.O. Cifuente, A. Marina, I. Budde, T.A. Mast, M. Sulewska, M. Berger, F.F.R. Buettner, T.L. Lowary, C. Whitfield, J.D.C. Codee, M. Schubert, M.E. Guerin, and T. Fiebig. 2024. Transition transferases prime group 2 capsular polysaccharide biosynthesis in Gram-negative bacteria. Nature Chemical Biology, https://doi.org/10.1038/s41589-024-01664-8

Kelly, S.D., O.G. Ovchinnikova, F. Müller, M. Steffen, M. Braun, R.P. Sweeney, M.  Kowarik, R Follador, T.L. Lowary, F. Serventi, and C. Whitfield. 2023. Discovery of  a previously unrecognized glycoform of the clinically prevalent O1 antigen from  Klebsiella pneumoniae. Proceedings of the National Academy of Sciences USA,120:  e2301302120  https://www.pnas.org/doi/abs/10.1073/pnas.2301302120

Ovchinnikova, O.G., L.P. Treat, T. Teelucksingh, B.R. Clarke, T.A. Miner, C. Whitfield, K.A.  Walker, and V.L. Miller. 2023. Hypermucoviscosity regulator RmpD interacts with Wzc and controls capsular polysaccharide chain length. MBio 14: 00800-23 https://journals.asm.org/doi/full/10.1128/mbio.00800-23?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org

Carfrae, L.A., K. Rachwalski, S. French, L. Seidel, C.N .Tsai, M.M Tu, C.R MacNair, O.G. Ovchinnikova, C Whitfield, and E.D Brown. Inhibiting fatty acid biosynthesis overcomes colistin resistance in mcr-1 expressing Enterobacteriaceae. Nature Microbiology, 8: 1026-1038 https://www.nature.com/articles/s41564-023-01369-z

Doyle, L., O.G. Ovchinnikova, B.-S. Huang, T.J.B. Forrester, T.L. Lowary, M.S. Kimber, and C. Whitfield. 2023. Mechanism and linkage specificities of the dual retaining β-Kdo glycosyltransferase modules of KpsC from bacterial capsule biosynthesis. Journal of Biological Chemistry 299:104609 https://www.jbc.org/article/S0021-9258(23)00251-X/fulltext

Weckener, M., L.S Woodward, B.R. Clarke, H. Liu, P.N. Ward, A. Le Bas, D. Bhella, C. Whitfield, and J.H. Naismith. 2023. The lipid linked oligosaccharide polymerase Wzy and itsregulating co-polymerase, Wzz, from enterobacterial common antigen biosynthesis form a complex. Open Biology 13: doi/10.1098/rsob.220373 https://royalsocietypublishing.org/doi/full/10.1098/rsob.220373?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org

Forrester, T.J.N., O.G. Ovchinnikova, Z. Li, E.N. Kitova, J.T. Nothof, A. Koizumi, J.S. Klassen, T.L. Lowary, C. Whitfield and M.S. Kimber. 2022. The retaining β-Kdo glycosyltransferase WbbB uses a double-displacement mechanism with an intermediate adduct rearrangement step. Nature Communications 13: 6277 https://www.nature.com/articles/s41467-022-33988-1

Liston, S.D., O.G. Ovchinnikova, O.G., M.S. Kimber, and C. Whitfield, C. A  2022. dedicated C-6 β-hydroxyacyltransferase required for biosynthesis of the glycolipid anchor for Vi antigen capsule in typhoidal Salmonella. Journal of Biological Chemistry 298: 102520 https://www.jbc.org/article/S0021-9258(22)00963-2/fulltext

Kelly, S.D, D.M. Williams, J.T. Nothof, T. Kim, T.L. Lowary, M.S. Kimber, and C. Whitfield. 2022. The biosynthetic origin of ribofuranose in bacterial polysaccharides. Nature Chemical Biology 18: 530-537. https://www.nature.com/articles/s41589-022-01006-6

Wear, S.S, C. Sande, O.G. Ovchinnikova, A. Preston, and C. Whitfield 2021. Investigation of core machinery for biosynthesis of Vi antigen capsular polysaccharides in Gram-negative bacteria. Journal of Biological Chemistry 298: 101486 https://www.jbc.org/article/S0021-9258(21)01295-3/fulltext

Sande, C, and C. Whitfield. 2021. Capsules and extracellular polysaccharides in Escherichia coli and Salmonella. EcoSalPlus. 2021. ESP-0033-2020 https://journals.asm.org/doi/10.1128/ecosalplus.ESP-0033-2020

Yang, Y., J. Liu, B.R. Clarke, L. Seidel, J.R. Bolla, P. Zhang, C.V. Robinson, C. Whitfield, and J.H. Naismith. 2021.  The molecular basis of regulation of bacterial capsule assembly by Wzc. Nature Communications 12: 4349.  https://www.nature.com/articles/s41467-021-24652-1

Whitfield, C., S.S. Wear and C. Sande. 2020. Assembly of bacterial capsular polysaccharides and exopolysaccharides. Annual Review of Microbiology 74: 521-543 https://www.annualreviews.org/doi/abs/10.1146/annurev-micro-011420-075607

Whitfield, C., DM. Williams, and S.D. Kelly. 2020. Lipopolysaccharide O antigens – bacterial glycans made to measure. Journal of Biological Chemistry 295: 10593-10609 https://www.jbc.org/article/S0021-9258(17)50100-3/fulltext

Clarke, B.R., O.G. Ovchinnikova, R.P. Sweeney, E. Kamski-Hennekam, R. Gitalis, E. Mallette, S.D. Kelly, T.L. Lowary, M.S. Kimber, and C. Whitfield. 2020. A bifunctional O-antigen polymerase structure reveals a new family of galactofuranosyltransferases. Nature Chemical Biology 16: 450-457 https://www.nature.com/articles/s41589-020-0494-0

Wear, S., B. Hunt, B.R. Clarke, and C. Whitfield. 2020. Characterization of the WbbF synthase required for the production of the Salmonella O:54 antigen. Journal of Bacteriology 202: e00625-19 https://journals.asm.org/doi/10.1128/JB.00625-19

Mann, E., S.D. Kelly, M.S. Al-Abdul-Wahid, B.R. Clarke, O.G. Ovchinnikova, B. Liu and C. Whitfield. 2019. Substrate recognition by a carbohydrate-binding module in the prototypical ABC transporter for lipopolysaccharide O antigen from Escherichia coli O9a. Journal of Biological Chemistry 294: 14978-14990. https://www.jbc.org/article/S0021-9258(20)34955-3/fulltext

Kelly, S.D., B.R. Clarke, O.G. Ovchinnikova, R.P Sweeney, M.L. Williamson, T.L. Lowary, and C. Whitfield. 2019. Klebsiella pneumoniae O1 and O2ac antigens provide prototypes for an unusual strategy for polysaccharide antigen diversification. Journal of Biological Chemistry. 294: 10863-10876 https://www.jbc.org/article/S0021-9258(20)30188-5/fulltext

Sande, C., C. Bouwman, E. Kell, N.N. Nickerson, S.B. Kapadia, and C. Whitfield. 2019. OPX proteins from the two major capsule assembly pathways present in Escherichia coli differ in structure and properties. Journal of Bacteriology. 201: e00213-19. https://journals.asm.org/doi/10.1128/JB.00213-19?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Doyle, L., O.G. Ovchinnikova, K. Myler, E. Mallette, B-S. Huang, T.L. Lowary, M.S. Kimber, and C. Whitfield. 2019. Biosynthesis of a conserved glycolipid anchor for Gram-negative bacterial capsules. Nature Chemical Biology. 15: 632-640. https://www.nature.com/articles/s41589-019-0276-8

Gao, Z. O.G. Ovchinnikova, B-S. Huang, F. Liu, D.E. Williams, R.J. Andersen, T.L. Lowary, C. Whitfield, and S.G Withers. 2019. A high-throughput “FP-tag” assay for the identification of glycosyltransferase inhibitors. Journal of American Chemical Society: 141: 2201-2204. https://pubs.acs.org/doi/10.1021/jacs.8b10940

Mann, E., S.D. Kelly, M.S. Al-Abdul-Wahid, B.R. Clarke, O.G. Ovchinnikova, B. Liu and C. Whitfield. 2019. Substrate recognition by a carbohydrate-binding module in the prototypical ABC transporter for lipopolysaccharide O antigen from Escherichia coli O9a. Journal of Biological Chemistry 294: 14978-14990 https://www.jbc.org/article/S0021-9258(20)34955-3/fulltext

Liston, S.D., S.A. McMahon, A. Le Bas, M.D. Suits, J.H. Naismith, and C. Whitfield. 2018. A periplasmic depolymerase provides new insight into ABC transporter-dependent secretion of bacterial capsular polysaccharides. Proceedings of the National Academy of Sciences USA 115: E4870-4879 https://www.pnas.org/doi/abs/10.1073/pnas.1801336115?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed

Clarke, B.R., O.G. Ovchinnikova, S.D. Kelly, M.L. Williamson, J.E. Butler, B. Liu, L. Wang, X. Gou, R. Follador, T.L. Lowary, and C. Whitfield. 2018. Molecular basis for the structural diversity in serogroup O2-antigen polysaccharides in Klebsiella pneumoniae. Journal of Biological Chemistry 293: 4666-4679 https://www.jbc.org/article/S0021-9258(20)39771-4/fulltext

Bi, Y., E. Mann, C. Whitfield, and J. Zimmer. 2018. Architecture of a channel-forming O-antigen polysaccharide ABC transporter. Nature 553: 361-365 https://www.nature.com/articles/nature25190

Diao J., C. Bouwman, D. Yan, J. Kang, A.K. Katakam, P. Liu, H. Pantua, A.R. Abbas, N.N. Nickerson, C. Austin, M. Reichelt, W. Sandoval, M. Xu, C. Whitfield, and S.B. Kapadia. 2017. Peptidoglycan association of murein lipoprotein is required for KpsD-dependent group 2 capsular polysaccharide expression and serum resistance in a uropathogenic Escherichia coli isolate. mBio 8: e00603-e00617 https://journals.asm.org/doi/10.1128/mBio.00603-17?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

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. Pentamidine sensitizes Gram-negative pathogens to antibiotics and overcomes acquired colistin resistance. Nature Microbiology 2: 17028 https://www.nature.com/articles/nmicrobiol201728

Williams, D.M., O.G. Ovchinnikova, A. Koizumi, I.L. Mainprize, M.S. Kimber, T.L. Lowary, and C. Whitfield. 2017. Single polysaccharide assembly protein that integrates polymerization, termination and chain-length quality control. Proceedings of the National Academy of Sciences USA 114: E1215-E1223 https://www.pnas.org/doi/10.1073/pnas.1613609114?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

  • MICR*4520 Microbial Cell Biology

Dr. Whitfield is no longer taking graduate students.

Graduate Students

  • Sarah Milinkovich (PhD) (coadvised by Dr. Khursigara)

Postdocs and Research Associates

  • Brad Clarke
  • Taylor Forrester (co-advised by Dr. Kimber)
  • Agnieska Kowalczyk

Research Technicians

  • Michelle Agyare-Tabbi
  • Noah Kuehfuss