Undermining the foundations of bacterial resistance

Scientists from the University of Guelph have used the Canadian Light Source (CLS) at the University of Saskatchewan to better understand how several infectious bacteria, including E. coli., build a protective sugar-based barrier that helps cloak their cells.

Published in the Journal of Biological Chemistry, the Guelph research provides the very early steps toward new treatments for E. coli and a whole range of bacteria. Their particular focus is on strains of E. coli that cause urinary tract and bloodstream infections, particularly those that are antibiotic resistant.

The research is looking to understand the enzyme that many infectious bacteria use to build the foundations of their protective capsule. The capsule helps shield the bacterium from attack by the human immune system and exists in many clinically distinct variants.

Making vaccines or drugs that targets the capsule itself directly is impractical as such treatments would target only a few bacteria. Instead, the Guelph team is focused on a key enzyme that builds the capsule foundation. This foundation could serve as a common point of attack, allowing a single treatment for several key pathogens infecting humans and livestock.

“We are interested in the machinery that builds the bacterium’s protective layer,” said Dr. Chris Whitfield, Professor Emeritus in the Department of Molecular and Cellular Biology. “By understanding and targeting the machinery, we can render the pathogen unable to survive in the host,”

Dr. Matthew Kimber, the team’s lead structural biologist, has often used the CLS to better understand how important proteins work. “For us, the CLS is absolutely essential. In this case, we could observe individual atoms; you cannot get that level of detail using laboratory sources.”

Whitfield and Kimber said their work would not have been possible without the longstanding collaboration between their labs and the research group of Todd Lowary, formerly at the University of Alberta and now located at Academica Sinica, Taiwan, and the National Taiwan University. Lowary’s group of carbohydrate chemists synthesized precise sugar-containing compounds critical for this research.

The research was performed by graduate students and postdoctoral researchers in Whitfield’s, Kimber’s and Lowary’s groups, and the project was funded through Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Glycomics Network.

Doyle, Liam, Olga G. Ovchinnikova, Bo-Shun Huang, Taylor JB Forrester, Todd L. Lowary, Matthew S. Kimber, and Chris Whitfield. "Mechanism and linkage specificities of the dual retaining β-Kdo glycosyltransferase modules of KpsC from bacterial capsule biosynthesis." Journal of Biological Chemistry (2023): 104609. https://doi.org/10.1016/j.jbc.2023.104609

Photos: Canadian Light Source | CMCF Beamline | Matthew Kimber, Chris Whitfield, and enzyme

Media Relations:

Greg Basky
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Canadian Light Source
306-657-3531
greg.basky@lightsource.ca