A new study by an international research team including University of Guelph scientists is the first to show how bacteria use a “molecular ruler” in making chains of sugar molecules for their protective coats like a tailor measuring fabric.

The finding might ultimately help in developing drugs to fight bacterial infections, said Prof. Chris Whitfield, Department of Molecular and Cellular Biology. He worked on the study with Guelph research associate Bradley Clarke and researchers in the United Kingdom and Germany.

Their paper appears this week in Nature Structural and Molecular Biology.

This study is the first to show how bacteria make a molecular ruler – actually a coiled protein complex — that is critical for protecting some bacterial invaders from their host’s immune system, said Whitfield.

Scientists have suspected for decades that bacteria used a molecular ruler or a timing mechanism to control the length of sugar polymer chains. Earlier work by Guelph researchers pointed to the former, but no one had seen the ruler or how it worked.

The researchers used crystallography and small-angle X-ray scattering to determine the structure of the ruler, which consists of three protein strands twisted together. Whitfield’s team then showed how genetically altering the length of the ruler itself affected the ability of E. coli bacteria to make sugar polymers.

The ruler enables bacteria to measure the length of growing polymer chains of sugars. Right-sized chains are then added to the microbe’s protective outer coat. Calling the ruler part of the microbe’s quality control system, Whitfield said, “It’s an elegant answer to a challenging problem faced by a wide range of biological systems, not just bacteria.”

He stresses this is fundamental research, but says the work might ultimately help researchers develop new drugs to fight infection by interfering with the ruler itself.

Learning about this structure might also help in investigating similar length-regulating mechanisms for making other cellular molecules and structures.

This research is part of a long-term Guelph collaboration with colleagues at the University of St. Andrews in the U.K. that “brings complementary technical experience and perspectives to examine a fascinating biological question.”

Their work was funded by the Natural Sciences and Engineering Research Council of Canada and by a Wellcome Trust Senior Investigator Award to Whitfield’s U.K. collaborator, James Naismith. Whitfield holds a Canada Research Chair in Molecular Microbiology.

Prof. Chris Whitfield
Department of Molecular and Cellular Biology
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