Basic principles of the virulence of Cryptococcus

Among fungal pathogens, Cryptococcus neoformans has gained great importance among the scientific community of several reasons. This fungus is the causative agent of cryptococcosis, a disease mainly associated to HIV immunosuppression and characterized by the appearance of meningoencephalitis. Cryptococcal meningitis is responsible for hundreds of thousands of deaths every year. Research of the pathogenesis and virulence mechanisms of this pathogen has focused on three main different areas: Adaptation to the host environment (nutrients, pH, and free radicals), mechanism of immune evasion (which include phenotypic variations and the ability to behave as a facultative intracellular pathogen), and production of virulence factors. Cryptococcus neoformans has two phenotypic characteristics, the capsule and synthesis of melanin that have a profound effect in the virulence of the yeast because they both have protective effects and induce host damage as virulence factors. Finally, the mechanisms that result in dissemination and brain invasion are also of key importance to understand cryptococcal disease. In this review, I will provide a brief overview of the main mechanisms that makes C. neoformans a pathogen in susceptible patients. Abbreviations: RNS: reactive nitrogen species; BBB: brain blood barrier; GXM: glucuronoxylomannan; GXMGal: glucuronoxylomannogalactan.O.Z. is funded by grants SAF2014-54336-R and SAF2017-86192-R1 from the Spanish Ministry for Economics, Industryand Competitivity. The author has no conflict of interest todeclare; Ministerio de Economía, Industria y Competitividad,Gobierno de España [SAF2017-86192-R1];Ministerio deEconomía, Industria y Competitividad, Gobierno de España[SAF2014-54336R].S