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Toxin Hunter Wages War on Bacteria A

s t h e n u m b e r of antibioticresistant bacteria continues to grow,

researchers in the Department of Molecular and Cellular Biology are developing new ways to fight these pathogens. Diseasecausing bacteria have long plagued humanity, and their ability to pass on antibioticresistant genes means that researchers need to stay one step ahead. “Bacterial pathogens use a variety of different methods to affect the host or the target,” says Rob Fieldhouse, a PhD candidate supervised by Prof. Rod Merrill. Protein toxins are one of the weapons in the bacterial arsenal. Cholera, diphtheria and pertussis toxins modify intracellular proteins, which kills the cell. Some toxins affect signalling molecules, while others affect the cell’s cytoskeleton. “One of the overall goals of the lab is to combat antibiotic resistance using small molecules,” says Fieldhouse. “One of the strategies is instead of trying to kill the whole organism, you just disarm it.You take away the weaponry without actually killing the pathogen.” This approach is complementary to more traditional vaccination strategies in which inactivated toxins help the body

Rob Fieldhouse

recognize and attack the real toxins. A self-described “toxin hunter,” Field-

The researchers use X-ray crystallog-

cereus, and Chelt, a toxin produced by Vibrio

house uses fold recognition technology to

raphy to identify structural characteristics

cholerae. The researchers believe Certhrax

find and identify new toxins by comparing

by aiming X-rays at toxin crystals, which

enters the target cell like other toxins, but

new sequences to toxin structures that have

produce patterns that yield key structural

kills in another way, while Chelt has a

already been characterized. “Knowing the

information. The lab team, which includes

different way of getting in. “We think it kills

structure of the toxin will help you design

technician Dawn White and postdoctoral

in a very traditional way, but we think it has

inhibitors for the toxin,” he says. “If you can

fellow Amanda Rochon, also tests the toxins

a new entry mechanism,” says Fieldhouse.

figure out that structural problem, then you

in yeast to see if the cells live or die.

The research is funded by the Natural Sci-

can start to work on the second problem,

Most recently, the lab is studying the

ences and Engineering Research Council,

which is to come up with a small molecule

disease-causing mechanisms of Certhrax,

the Canadian Institutes of Health Research

that will bind the toxin and inactivate it.”

an anthrax-like toxin produced by Bacillus

and the Human Frontier Science Program.

Zygote Plus 4 Fall 2011

Toxin Hunter WagesWar on Bacteria