PubMed · 13290768
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P MONNET, P F BLANC. 1955-12-06. [Human cryptococcosis].. https://pubmed.ncbi.nlm.nih.gov/13290768/
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In the past 2 decades, Cryptococcus has emerged in its clinical significance and as a model yeast for understanding molecular pathogenesis. C neoformans and C gattii are currently considered major primary and secondary pathogens in a wide array of hosts that are known to be immunocompromised or apparently immunocompetent. A recent outbreak of C gattii infections further underscores the clinical importance of the yeast through its epidemiology and pathogenicity features. With an enlarging immunosuppressed population caused by HIV infection, solid organ transplantation, and clinical use of potent immunosuppressives, such as cancer chemotherapy, monoclonal antibodies, and corticosteroids, this fungus has become a well-established infectious complication of modern medicine. This article examines current issues in cryptococcal infections, including new classification, epidemiology, pathogenesis, and specific clinical aspects.
The use of insertional mutagenesis to discover genes that impact laccase activity has resulted in the identification of multiple cellular processes that affect the fitness of Cryptococcus neoformans. Fitness has been defined as the ability of an organism to propagate and evolve within a given environment. Because the human host is an evolutionary dead-end for an opportunistic pathogen, we have defined pathogenic fitness here as the capability to successfully propagate within the stressful environment of the host, causing disease by expression of virulence traits that damage the host. In this review, laccase-deficient insertional mutants will be highlighted in terms of the basic biological processes in which they are involved. The impact of laccase-associated cellular functions on fitness and virulence will be discussed, as will the mutants' potential as therapeutic targets. Vacuolar function, copper homeostasis, mitochondrial function and carbon repression are covered.
Proton nuclear magnetic resonance spectroscopy is a nondestructive technique that identifies chemicals in solution and in living cells. It has been used in cryptococcal research to identify the primary structure of capsular glucuronoxylomannans, link cellular apoptosis susceptibility (CAS) genes to positioning of residues on the mannose backbone of glucuronoxylomannan, and verify that the cryptococcal virulence determinant, phospholipase B, is elaborated in vivo. Promising clinical applications include speciation (Cryptococcus neoformans and Cryptococcus gattii), with preliminary evidence that varieties neoformans and grubii can also be distinguished, non-invasive diagnosis of cerebral cryptococcomas, and, in cases of meningitis, monitoring therapeutic response by analysis of cerebrospinal fluid.