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Review
. 2012 Jan;36(1):78-94.
doi: 10.1111/j.1574-6976.2011.00286.x. Epub 2011 Jul 4.

Profiling a killer, the development of Cryptococcus neoformans

Lukasz Kozubowski  1 , Joseph Heitman
Affiliations
Review

Profiling a killer, the development of Cryptococcus neoformans

Lukasz Kozubowski et al. FEMS Microbiol Rev. 2012 Jan.

Abstract

The ability of fungi to transition between unicellular and multicellular growth has a profound impact on our health and the economy. Many important fungal pathogens of humans, animals, and plants are dimorphic, and the ability to switch between morphological states has been associated with their virulence. Cryptococcus neoformans is a human fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised and, in some cases, immunocompetent hosts. Cryptococcus neoformans grows vegetatively as a budding yeast and switches to hyphal growth during the sexual cycle, which is important in the study of cryptococcal pathogenicity because spores resulting from sexual development are infectious propagules and can colonize the lungs of a host. In addition, sexual reproduction contributes to the genotypic variability of Cryptococcus species, which may lead to increased fitness and virulence. Despite significant advances in our understanding of the mechanisms behind the development of C. neoformans, our knowledge is still incomplete. Recent studies have led to the emergence of many intriguing questions and hypotheses. In this review, we describe and discuss the most interesting aspects of C. neoformans development and address their impact on pathogenicity.

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Figures

Fig. 1
Fig. 1
Sexual cycle of Cryptococcus neoformans. During the opposite-sex mating, a and α haploid yeast cells secrete peptide pheromones that stimulate cell–cell fusion. The resulting zygote develops first as hyphae, which are dikaryotic. After the first clamp cell is formed, a narrow ‘pioneer’ hypha is present at the apex. During hyphal growth, a basidium develops from the apical cell. Nuclear fusion and meiosis take place most likely concomitant with the formation of the basidium. Postmeiotic nuclei undergo rounds of mitotic divisions and four chains of spores are formed by subsequent budding from the surface of the basidium. Alternatively, a and α haploid yeast cells can form an a/α diploid, which grows as yeast at 37 °C in a rich medium and forms hyphae at 24 °C on mating-inducing medium. These diploid-derived hyphae are monokaryotic, have unfused clamp cells, and produce a and α spores. During same-sex mating, two yeast cells of the same mating type (α is depicted) undergo fusion and form monokaryotic hyphae with haploid nuclei. Concomitant with the formation of the basidium, nuclear fusion and meiosis occur. The resulting recombinant spores are of a single mating type. A single yeast cell can undergo autopolyploidization (i.e. endoreplication), resulting in a diploid, which develops into monokaryotic hyphae with diploid nuclei and unfused clamp cells. Autopolyploidization can also occur in the hyphae. Both opposite- and same-sex mating hyphae can develop chlamydospores and blastospores (not depicted) (see the text for a more detailed description).
Fig. 2
Fig. 2
The pheromone response pathway in Cryptococcus neoformans. Other pathways that either positively regulate sexual development (cAMP-PKA pathway, Ca2+-calcineurin pathway) or inhibit mating (light sensing, stress sensing) are also indicated (see the text for details).
Fig. 3
Fig. 3
Postmating hyphae (a) of Cryptococcus neoformans serotype A and basidia (b) imaged by scanning electron microscopy. Images were taken by Lukasz Kozubowski (a) and Soo Chan Lee (b) and Valerie Knowlton (a, b).
See this image and copyright information in PMC

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