Capsule biogenesis of Cryptococcus neoformans
Hans de Cock, Jan Grijpstra
Cryptococcus neoformans is a yeast-like fungus that belongs to the basidiomycetes. It is an opportunistic human pathogen with worldwide distribution that can cause chronic infections. The incidence of cryptococcosis is rising with the AIDS epidemic and the use of immunosupressive drugs. Upon inhalation, small yeast cells are able to penetrate deeply into the lungs were they are either cleared from or are able to survive and invade the human body. Once inside the body it is able to spread and to cause infections or to hide. It has a preference for the central nervous system resulting in life-threatening meningitis (More info at this site).
One of the most important virulence factors of Cryptococcus is its polysaccharide capsule that surrounds the cell. Capsule consists of two polysaccharides named GXM and Gal-XM. Four serotypes can be distinguished (A, B, C and D) based on the capsule polysaccharide structure of GXM. The capsule has many different modulating effects on the host immune system and plays an important role in the intracellular survival of Cryptococcus in macrophages, which together adds to the ability to be a successful pathogen. Although this capsule is one of the most important virulence factors, it is not yet known how it is synthesized and assembled. Only a few genes have been identified and been shown to affect capsule biogenesis when mutated. Among those are 4 CAP genes (CAP 10, 59, 60 & 64) with unknown cellular location and function in capsule biogenesis. Our research is focussing on the role of the CAP proteins in capsule biogenesis at a molecular level.