Sugars are toxic in excess because they are highly reactive. But we don’t normally think of them as toxic to bacteria. Bacteria thrive by eating sugars.
I was reading “TB or Not TB?” at The Scientist and was amused at this anecdote, about efforts to find new ways to kill drug-resistant TB:
Rainer Kalscheuer, now at Heinrich-Heine University in Germany, was searching for genes and proteins that made some TB cells more treatment tolerant than others. After doing a microarray analysis, Kalscheuer wanted to investigate a metabolic intermediate enzyme called GlgE, but Jacobs balked. “I told him a group at Harvard had already shown that glgE was an essential gene that can’t be manipulated,” Jacobs remembers. But Kalscheuer persevered and found out that glgE could be knocked out and studied if grown in the right culture medium.
Note for grammarians: glgE is the gene, GlgE is the protein.
The key to creating viable glgE knockout strains turned out to be trehalose, a cell wall carbohydrate. TB bacteria that lacked glgE died instantly when trehalose was present, but survived if it was removed. The Harvard group had used medium that contained trehalose without realizing it because the carbohydrate, used as a preservative, was an unlisted ingredient.
This is the kind of thing that drives impatient biologists crazy. Experiments are so sensitive to subtle variations, such as an unlisted preservative in the culture medium, that Biology smiles only on those who are exceedingly careful, thoughtful, and patient with tedious troubleshooting. Also, those who don’t put too much faith in the results of their peers!
The next step for Kalscheuer and Jacobs was figuring out the functional relationship between the two proteins. GlgE had been implicated in glycogen metabolism, but the connection with trehalose was unclear. Finally, after a painstaking series of suppressor genetics experiments, they elucidated the biochemical pathway: Glycogen and glucose produce trehalose; an enzyme known as trehalose synthase converts the trehalose into maltose; then, the maltose becomes maltose-1-phosphate, the protein that GlgE converts into glucan. When glgE is knocked out, maltose-1-phosphate accumulates, which kills the tuberculosis bacterium.
Turnabout is fair play. It seems only fitting that bacteria should die from high-carb diet toxicity. Why should humans be the only ones?