Abstract
Cryptococcus neoformans is a human fungal pathogen that causes lethal infections of the lung and central nervous system in immunocompromised individuals. C. neoformans has a defined bipolar sexual life cycle with a and α mating types. During the sexual cycle, which can occur between cells of opposite mating types (bisexual reproduction) or cells of one mating type (unisexual reproduction), a dimorphic transition from yeast to hyphal growth occurs. Hyphal development and meiosis generate abundant spores that, following inhalation, penetrate deep into the lung to enter the alveoli, germinate, and establish a pulmonary infection growing as budding yeast cells. Unisexual reproduction has been directly observed only in the Cryptococcus var. neoformans (serotype D) lineage under laboratory conditions. However, hyphal development has been previously associated with reduced virulence and the serotype D lineage exhibits limited pathogenicity in the murine model. In this study we show that the serotype D hyperfilamentous strain XL280α is hypervirulent in an animal model. It can grow inside the lung of the host, establish a pulmonary infection, and then disseminate to the brain to cause cryptococcal meningoencephalitis. Surprisingly, this hyperfilamentous strain triggers an immune response polarized towards Th2-type immunity, which is usually observed in the highly virulent sibling species C. gattii, responsible for the Pacific Northwest outbreak. These studies provide a technological advance that will facilitate analysis of virulence genes and attributes in C. neoformans var. neoformans, and reveal the virulence potential of serotype D as broader and more dynamic than previously appreciated.
Highlights
Cryptococcus neoformans is an opportunistic fungal pathogen that is distributed worldwide
Phenotypic characterization of XL280 To investigate the impact of hyphal development during unisexual reproduction we utilized the serotype D hyperfilamentous strain XL280a
XL280a was at a significantly higher abundance in the brain at both time points, while JEC21 infection was cleared from the CNS by four weeks post infection (Figure 3A). These results indicate that XL280a and JEC21a are both capable of surviving and replicating inside the host; XL280a more successfully establishes an infection in the lung and disseminates to the central nervous system to cause meningoencephalitis
Summary
Cryptococcus neoformans is an opportunistic fungal pathogen that is distributed worldwide. Pathogenic Cryptococcus lineages comprise two main species: Cryptococcus neoformans and Cryptococcus gattii. C. neoformans is classified into two varieties: var. The serotype A variety is the most common cause of infection, typically of the central nervous system in immunocompromised individuals, including organ-transplant patients and HIV-infected individuals. Cryptococcal meningitis is an AIDS-defining illness in 30% of HIV/AIDS presentations and it is a major cause of mortality in AIDS patients in HIV/AIDS endemic regions, such as Southeast Asia and Sub-Saharan Africa [1,2]. C. gattii infects healthy individuals and is responsible for the ongoing Cryptococcus outbreak on Vancouver
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
