Cryptococcus neoformans
Research Article | Host-Microbe BiologyA Heat-Killed Cryptococcus Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine ModelInvasive fungal infections kill more than 1.5 million people each year, with limited treatment options. There is no vaccine available in clinical use to prevent and control fungal infections. Our recent studies showed that a mutant of the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase in Cryptococcus neoformans, elicited superior protective Th1 host immunity...
Research Article | Host-Microbe BiologyTranslational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen Cryptococcus neoformansFungal survival in a mammalian host requires the coordinated expression and downregulation of a large cohort of genes in response to cellular stresses. Initial infection with C. neoformans occurs in the lungs, where it interacts with host macrophages. Surviving macrophage-derived cellular stresses, such as the production of reactive oxygen and nitrogen species, is...
Observation | Host-Microbe BiologyHost Carbon Dioxide Concentration Is an Independent Stress for Cryptococcus neoformans That Affects Virulence and Antifungal SusceptibilityA number of studies comparing either patient outcomes or model system virulence across large collections of Cryptococcus isolates have found significant heterogeneity in virulence even among strains with highly related genotypes. Because this heterogeneity cannot be explained by variations in the three well-characterized virulence traits (growth at host body temperature, melanization, and polysaccharide capsule formation), it...
Research Article | Host-Microbe BiologyPulmonary Iron Limitation Induced by Exogenous Type I IFN Protects Mice from Cryptococcus gattii Independently of T CellsCryptococcus neoformans and Cryptococcus gattii cause fatal infection in immunodeficient and immunocompetent individuals. While these fungi are sibling species, C. gattii infects very few AIDS patients, while...
Research Article | Host-Microbe BiologyCryptococcus neoformans Glucuronoxylomannan and Sterylglucoside Are Required for Host Protection in an Animal Vaccination ModelThe number of deaths from cryptococcal meningitis is around 180,000 per year. The disease is the second leading cause of mortality among individuals with AIDS. Antifungal treatment is costly and associated with adverse effects and resistance, evidencing the urgency of development of both therapeutic and prophylactic tools. Here we demonstrate the key roles of polysaccharide- and glycolipid-containing structures in a vaccination model to...
Research Article | Host-Microbe BiologyCdk8 and Ssn801 Regulate Oxidative Stress Resistance and Virulence in Cryptococcus neoformansCryptococcus neoformans is a fungal pathogen that primarily affects severely immunocompromised patients, resulting in 200,000 deaths every year. This yeast occurs in the environment and can establish disease upon inhalation into the lungs of a mammalian host. In this harsh environment it must survive engulfment by host phagocytes, including the oxidative stresses it...
Research Article | Host-Microbe BiologyTranscriptional Profiling of Patient Isolates Identifies a Novel TOR/Starvation Regulatory Pathway in Cryptococcal VirulenceCryptococcus is a fungal pathogen that kills an estimated quarter of a million individuals yearly and is the most common cause of nonviral meningitis in the United States. The fungus is carried in about 10% of the adult population and, after reactivation, causes disease in a wide variety of immunosuppressed individuals, including the HIV infected and patients...
Research Article | Host-Microbe BiologyMaintenance of Mitochondrial Morphology in Cryptococcus neoformans Is Critical for Stress Resistance and VirulenceC. neoformans is a yeast that causes fatal brain infection in close to 200,000 people worldwide every year, mainly afflicting individuals with AIDS or others who are severely immunocompromised. One feature of this microbe that helps it cause disease is that it is able to withstand toxic molecules it encounters when host cells engulf it in their efforts to control the...
- Research ArticleUDP-Glucuronic Acid Transport Is Required for Virulence of Cryptococcus neoformans
Cryptococcus neoformans causes lethal meningitis in almost two hundred thousand immunocompromised patients each year. Much of this fungal pathogen’s ability to resist host defenses and cause disease is mediated by carbohydrate structures, including a complex polysaccharide capsule around the cell. Like most eukaryotic glycoconjugates, capsule polysaccharides are made within the secretory pathway, although their precursors are...