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      Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review

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          Abstract

          The genus Cryptococcus contains two primary species complexes that are significant opportunistic human fungal pathogens: C. neoformans and C . gattii. In humans, cryptococcosis can manifest in many ways, but most often results in either pulmonary or central nervous system disease. Patients with cryptococcosis can display a variety of symptoms on a spectrum of severity because of the interaction between yeast and host. The bulk of our knowledge regarding Cryptococcus and the mechanisms of disease stem from in vitro experiments and in vivo animal models that make a fair attempt, but do not recapitulate the conditions inside the human host. To better understand the dynamics of initiation and progression in cryptococcal disease, it is important to study the genetic and phenotypic differences in the context of human infection to identify the human and fungal risk factors that contribute to pathogenesis and poor clinical outcomes. In this review, we summarize the current understanding of the different clinical presentations and health outcomes that are associated with pathogenicity and virulence of cryptococcal strains with respect to specific genotypes and phenotypes.

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          Most cited references192

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          Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis.

          Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease.
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            Cryptococcus: from environmental saprophyte to global pathogen.

            Cryptococcosis is a globally distributed invasive fungal infection that is caused by species within the genus Cryptococcus which presents substantial therapeutic challenges. Although natural human-to-human transmission has never been observed, recent work has identified multiple virulence mechanisms that enable cryptococci to infect, disseminate within and ultimately kill their human host. In this Review, we describe these recent discoveries that illustrate the intricacy of host-pathogen interactions and reveal new details about the host immune responses that either help to protect against disease or increase host susceptibility. In addition, we discuss how this improved understanding of both the host and the pathogen informs potential new avenues for therapeutic development.
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              The Cryptococcus neoformans capsule: a sword and a shield.

              The human fungal pathogen Cryptococcus neoformans is characterized by its ability to induce a distinct polysaccharide capsule in response to a number of host-specific environmental stimuli. The induction of capsule is a complex biological process encompassing regulation at multiple steps, including the biosynthesis, transport, and maintenance of the polysaccharide at the cell surface. By precisely regulating the composition of its cell surface and secreted polysaccharides, C. neoformans has developed intricate ways to establish chronic infection and dormancy in the human host. The plasticity of the capsule structure in response to various host conditions also underscores the complex relationship between host and parasite. Much of this precise regulation of capsule is achieved through the transcriptional responses of multiple conserved signaling pathways that have been coopted to regulate this C. neoformans-specific virulence-associated phenotype. This review focuses on specific host stimuli that trigger the activation of the signal transduction cascades and on the downstream transcriptional responses that are required for robust encapsulation around the cell.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                J Fungi (Basel)
                J Fungi (Basel)
                jof
                Journal of Fungi
                MDPI
                2309-608X
                30 March 2021
                April 2021
                : 7
                : 4
                : 260
                Affiliations
                [1 ]Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC 27710, USA; Marhiah.Montoya@ 123456Duke.edu
                [2 ]Division of Infectious Diseases, Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA
                [3 ]Department of Biology, Duke University, Durham, NC 27710, USA; Paul.Magwene@ 123456Duke.edu
                Author notes
                [* ]Correspondence: John.Perfect@ 123456Duke.edu
                Author information
                https://orcid.org/0000-0002-6112-5531
                Article
                jof-07-00260
                10.3390/jof7040260
                8067209
                33808500
                3dca8559-9d76-4f5a-9812-2f9a3710ab3e
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 09 March 2021
                : 25 March 2021
                Categories
                Review

                cryptococcus,genotype,phenotype,virulence,cryptococcal meningitis,pulmonary cryptococcosis,clinical presentation,clinical outcomes

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