CHAPTER ONE The Tools for Virulence of Cryptococcus neoformans Carolina Coelho * ,† , Anamelia Lorenzetti Bocca } , Arturo Casadevall * ,1 * Department of Microbiology and Immunology, Albert Einstein College of Medicine of Yeshiva University, New York, USA † Centre for Neuroscience and Cell Biology of Coimbra, Institute of Microbiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal } Department of Cellular Biology, Institute of Biological Sciences, University of Brası ´lia, Brası ´lia, Brazil 1 Corresponding author: e-mail address: arturo.casadevall@einstein.yu.edu Contents 1. Introduction to Cryptococcus neoformans and Cryptococcosis 2 2. What Tools Allow C. neoformans to Become a Pathogen? 4 2.1 The host–pathogen duo and virulence as an emergent property 4 2.2 Thermotolerance 5 2.3 Acquisition of nutrients 5 2.4 Capsule 7 2.5 Melanin and laccase 12 2.6 Urease 13 2.7 Phospholipase 14 2.8 Oxidative defenses 14 2.9 Antiphagocytic protein 1 16 2.10 Other virulence factors 16 2.11 Secreted vesicles 16 2.12 Morphological changes 17 3. How Does C. neoformans Survive Within a Host? 18 3.1 Intracellular survival of C. neoformans 18 3.2 Nonlytic exocytosis 21 3.3 Dissemination: Penetration blood–brain barrier 21 3.4 Subversion of host immune response 23 4. Why Is C. neoformans Successful as a Pathogen? 24 5. Future Directions 26 References 28 Abstract Cryptococcus neoformans is a fungal pathogen that causes almost half a million deaths each year. It is believed that most humans are infected with C. neoformans, possibly in a form that survives through latency in the lung and can reactivate to cause disease if the host becomes immunosuppressed. C. neoformans has a remarkably sophisticated Advances in Applied Microbiology, Volume 87 # 2014 Elsevier Inc. ISSN 0065-2164 All rights reserved. http://dx.doi.org/10.1016/B978-0-12-800261-2.00001-3 1