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CNS disease represents a major interaction between the host and the yeast. In this regard, we have examined the myriads of tools that this group of yeasts possess that allow them to become very efficient pathogens in the human CNS, causing fatal meningoencephalitis if untreated. In the age of molecular approaches to the investiagion of fungal pathogenesis, cryptococcosis has been studied extensively at the genetic level, and there is an impressive array of virulence factors that this basidiomycetous pathogen has developed to cause disease. This review details a series of virulence factors and their pathways. There is also some appreciation of the complexity of the host responses, which are so essential to the outcome of these infections.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf496","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T11:54:06Z","timestamp":1758628446000},"page":"1265-1272","source":"Crossref","is-referenced-by-count":0,"title":["The Pain Is in the Brain With the Sugar-Coated Killer"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6411-198X","authenticated-orcid":false,"given":"Julia A","family":"Messina","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Duke University School of Medicine , Durham, North Carolina ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R","family":"Perfect","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Duke University School of 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