Although Cryptococcus neoformans and cryptococcosis have existed for several millennia, a century has passed since the discovery of this encapsulated yeast and its devastating disease. With the advent of the AIDS pandemic, cryptococcal meningitis has emerged as a leading cause of infectious morbidity and mortality and a frequently life-threatening opportunistic mycosis among patients with AIDS. Both basic and clinical research have accelerated in the 1990s, and this review attempts to highlight some of these advances. The discussion covers recent findings, current concepts, controversies, and unresolved issues related to the ecology and genetics of C. neoformans; the surface structure of the yeast; and the mechanisms of host defense. Regarding cell-mediated immunity, CD4+ T cells are crucial for successful resistance, but CD8+ T cells may also participate significantly in the cytokine-mediated activation of anticryptococcal effector cells. In addition to cell-mediated immunity, monoclonal antibodies to the major capsular polysaccharide, the glucuronoxylomannan, offer some protection in murine models of cryptococcosis. Clinical concepts are presented that relate to the distinctive features of cryptococcosis in patients with AIDS and the diagnosis, treatment, and prevention of cryptococcosis in AIDS patients.

Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans.

Cellular differentiation, mating, and filamentous growth are regulated in many fungi by environmental and nutritional signals. For example, in response to nitrogen limitation, diploid cells of the yeast Saccharomyces cerevisiae undergo a dimorphic transition to filamentous growth referred to as pseudohyphal differentiation. Yeast filamentous growth is regulated, in part, by two conserved signal transduction cascades: a mitogen-activated protein kinase cascade and a G-protein regulated cyclic AMP signaling pathway. Related signaling cascades play an analogous role in regulating mating and virulence in the plant fungal pathogen Ustilago maydis and the human fungal pathogens Cryptococcus neoformans and Candida albicans. We review here studies on the signaling cascades that regulate development of these and other fungi. This analysis illustrates both how the model yeast S. cerevisiae can serve as a paradigm for signaling in other organisms and also how studies in other fungi provide insights into conserved signaling pathways that operate in many divergent organisms.

Signal Transduction Cascades Regulating Fungal Development and Virulence

Polyphenol oxidases in plants. Recent progress

Summary
Melanins are enigmatic pigments that are produced by a wide variety of microorganisms including several species of pathogenic bacteria, fungi and helminthes. The study of melanin is difficult because these pigments defy complete biochemical and structural analysis. Nevertheless, the availability of new reagents in the form of monoclonal antibodies and melanin-binding peptides, combined with the application of various physical techniques, has provided insights into the process of melanization. Melanization is important in microbial pathogenesis because it has been associated with virulence in many microorganisms. Melanin appears to contribute to virulence by reducing the susceptibility of melanized microbes to host defence mechanisms. However, the interaction of melanized microbes and the host is complex and includes immune responses to melanin-related antigens. Production of melanin has also been linked to protection against environmental insults. Interference with melanization is a potential strategy for antimicrobial drug and pesticide development. The process of melanization poses fascinating problems in cell biology and provides a type of pathogenic strategy that is common to highly diverse pathogens.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1462-5814.2003.00268.x

The contribution of melanin to microbial pathogenesis.

Biosynthesis of fungal melanins and their importance for human pathogenic fungi.

A double mutant of Cryptococcus neoformans which lacked the ability to produce melanin (Mel-) on media containing diphenols and failed to grow at 37 degrees C (temperature sensitive, Tem-) was obtained by UV irradiation and subsequent cloning The mutant showed two lesions in melanogenesis in that it lacked the active transport system for diphenolic compounds and also lacked phenoloxidase Ultrastructures of the mutant and wild-type cells grown on a medium with or without L-dopa showed that only the wild-type cells grown on L-dopa medium formed a dark cell wall layer, presumably containing melanin The mutant was crossed with a wild type, and the phenotypes of the progeny were analyzed The analysis showed no linkage between the mating type and either Mel or Tem loci, but loose linkage was seen between Mel and Tem loci The progeny, Mel+ Tem+, Mel+ Tem-, Mel- Tem+, and Mel- Tem-, were studied for their virulence in mice Only Mel+ Tem+ types killed mice with an inoculum of 5 X 10(5) cells within 50 days Images

T J Popkin

Papers

Melanin-lacking mutants of Cryptococcus neoformans and their virulence for mice.