Peeling the onion: the outer layers of Cryptococcus neoformans

Abstract

Cryptococcus neoformans is an opportunistic fungal pathogen that is ubiquitous in the environment. It causes a deadly meningitis that is responsible for over 180,000 deaths worldwide each year, including 15% of all AIDS-related deaths. The high mortality rates for this infection, even with treatment, suggest a need for improved therapy. Unique characteristics of C. neoformans may suggest directions for drug discovery. These include features of three structures that surround the cell: the plasma membrane, the cell wall around it, and the outermost polysaccharide capsule. We review current knowledge of the fundamental biology of these fascinating structures and highlight open questions in the field, with the goal of stimulating further investigation that will advance basic knowledge and human health.

(A) Electron micrographs of Cryptococcus neoformans. Left, quick-freeze deep-etch image of cells grown in capsule-inducing conditions (as in Haynes et al. 2011); right, transmission image of cells grown in rich medium (YPD), which yields only thin capsules. C: capsule; W: cell wall; PM: plasma membrane; M: mitochondrion; O: outer cell wall layer; I: inner cell wall layer. (B) Fluorescent micrograph highlighting the cell wall and capsule. Cryptococcal cells were induced to form capsule and stained with florescein (green) to label the cell wall and monoclonal antibody 2H1 (blue, generously provided by Arturo Casadevall) to label the capsule, as in Pierini and Doering (2001). (C) Quick-freeze deep-etch image highlighting the two layers of the cell wall.