Novel role for a family of proteins present in the cell wall of a pathogenic yeast that helps it survive in the human host
16 Mar 2018
Dr. Rupinder Kaur, Senior Fellow
Centre for DNA Fingerprinting and Diagnostics, Hyderabad
Hospital-acquired invasive fungal infections, a major clinical challenge, are associated with high mortality rates. Candida species are the most common bloodstream fungal pathogens with Candida glabrata being the second most prevalent Candida species after C. albicans.
In our research group, we are interested in delineating the factors that help C. glabrata survive in the human host and establish infections. In this regard, we have previously shown that C. glabrata is able to survive and multiply in macrophages, which constitute the first line of human defense system. In our recently published work, we uncover a new role for a family of eleven aspartyl proteases, also known as yapsins, that are present at the surface of C. glabrata cells, in suppression of the host innate immune response.
Aspartyl proteases are enzymes that cleave peptides and proteins. We show that absence of aspartyl proteases results in activation of the inflammatory response in human macrophages and killing of C. glabrata cells. As cell wall is the first site, that is recognized by host immune cells, this immune activation is likely due to altered structure of the cell wall in the C. glabrata mutant lacking these proteases. Consistent with this, we found aspartyl proteases are required for maintenance of proper cell wall composition and architecture in C. glabrata.
Together, our findings demonstrate aspartyl proteases to be a potent weapon in the anti-host arsenal of C. glabrata which suppresses the host immune response and provides protection against macrophage-mediated killing.
Aspartyl proteases in Candida glabrata are required for suppression of the host innate immune response. Mubashshir Rasheed, Anamika Battu and Rupinder Kaur. Journal of Biological Chemistry. February 2018.
Banner image credit: Kevin Mackenzie, University of Aberdeen. Wellcome Images. False-coloured scanning electron micrograph of two macrophage cells four hours after infection with Candida yeast spores. The projections seen here extending from the macrohpages are candida hyphae growing within the cell. This will eventually kill the cells by causing them to burst. Macrophages are white blood cells of the immune system which engulf and destroy foreign material. They are found in all tissues of the body. Overgrowth of yeasts can result in fungal infections such as thrush (candidiasis). Horizontal image width is 65 microns.