We have all heard the verse, “a little bit of sugar makes the medicine go down.” And while a bit of sugar will make medicine more palatable, scientists at the university of Toronto have discovered that Candida albicans makes use of sugar to evade detection by the body’s immune system.
In the study, researchers used the Merck & Co. Candida albicans mutant library, recently made public and containing just about all the genes of the C. albicans genome. If not for the library, the team would have only been able to test around 10 percent of the genes.
Lead scientist professor Leah Cowen, who holds the Canada Research Chair in Microbial Genomics and Infectious Disease in U of T’s Department of Molecular Genetics said, “It really let us approach this pathogen from a holistic perspective and evaluate the role of all its genes in disease.”
The research team discovered a sugar molecule on the surface of the fungus cells that triggered death in our immune cells before they would have destroyed the fungal cells. They proved it wasn’t just a matter of the shape-change from a single cell to a long chain of cells that helped the fungus, but what was happening along with the shape-change.
Ingestion by macrophages
In the laboratory, immune cells, called macrophages, were allowed to consume, or engulf, the fungal cells. After 60 minutes, the dead fungal cells were removed from the macrophages. The team then exposed the dead fungal cells to new macrophages. A control group of fungal cells (not previously consumed by macrophages) were also exposed to new macrophages.
“The fungal cells that were never internalized by macrophages couldn’t kill the fresh macrophages, but those that had been inside a macrophage could kill beautifully,” says Cowen. With this important clue, the team surmised that the fungal cells that had been engulfed by the macrophages had somehow changed. It couldn’t be an internal change because dead cells have no active processes, so it had to be something on the surface of the cell.
Using an enzyme of Endo H, researchers snipped off the sugars from the glycosylated proteins on the surface of the dead fungal cells, Doing so completely blocked the ability of the fungus to kill. This discovery opens up possibilities in developing a new therapeutic method of dealing with Candida albicans.
Fungal infections kill more than 1.5 million people a year around the globe, and Candida albicans accounts for almost 90 percent of all hospital-acquired fungal infections, and in Canada, they are the third leading cause of bloodstream infections in ICUs.
This research was published in the journal Nature Communications on March 31, 2015. The title of the article: “Global analysis of fungal morphology exposes mechanisms of host cell escape.”
