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Glycosylated proteins on surface of C. albicans facilitate fungal growth
Contrary to previous beliefs, Candida albicans does not appear to require filamentation to escape the immune cells of its host, according to recent findings.
Instead, immune cell death is triggered by fungal wall remodeling due to glycosylated protein exposure, Leah Cowen, PhD, Canada research chair in microbial genomics and infectious disease at the University of Toronto, and colleagues wrote.
"It's not the shape-change per se that enables the fungus to kill the immune cell, but what happens along with it,” Cowen said in a press release. “The addition of glycosylated proteins, which are proteins with a sugar attached, remodels the surface of the fungal cells.”
Cowen and colleagues used a genome-scale C. albicans mutant library to evaluate the morphogenesis of the fungus. They identified 872 genes required for C. albicans morphogenesis in response to serum and 102 genes that encode filamentation repressors.
Interaction between C. albicans mutants blocked in filamentation and mammalian macrophages were analyzed. Mouse macrophages were inoculated with C. albicans cells, which then were removed. Researchers exposed new macrophages to fungal cells that had been consumed by macrophages and those that had not.
“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,” Cowen said in the release.
The researchers deduced that the change that enabled the dead fungal cells to kill macrophages was likely on their surface. They treated the cells with the enzyme Endo H glycosidase to remove glycoproteins from the cell surfaces. This alteration blocked the ability of the fungal cells to kill macrophages.
According to the researchers, these findings may spark development of new therapies to address C. albicans fungi, which account for almost 90% of nosocomial infections in the United States.
A therapeutic strategy that targets the ability of fungal cells to avoid the immune system would be beneficial because it might minimize the effects on healthy microbes and thwart drug resistance.
“If you develop a drug that targets something that’s only found in fungi, it’s less likely to have side effects in a human," Cowen said in the release. – by Jen Byrne
Disclosure: The researchers report no relevant disclosures.