Elucidating the Pathogenesis of Spores from the Human Fungal Pathogen<i>Cryptococcus neoformans</i>

Giles, Steven S.; Dagenais, Taylor R. T.; Botts, Michael R.; Keller, Nancy P.; Hull, Christina M.

doi:10.1128/iai.00334-09

Cited by 177 publications

(195 citation statements)

References 46 publications

Supporting

Mentioning

187

Contrasting

Unclassified

Order By: Relevance

“…We observed that yeast cells mixed with spores could be phagocytosed by macrophages when spores were also present. These observations confirm and extend the previously reported findings of Giles et al, who discovered that spores do not require opsonin to be phagocytosed by macrophages (15). We postulate that ␤-1,3-glucans on spores and acapsular yeast cells are readily exposed to dectin 1, leading to rapid phagocytosis by macrophages.…”

Section: Discussionsupporting

confidence: 82%

“…As positive and negative controls, unopsonized yeast cells and yeast cells opsonized with monoclonal antibody 18B7, respectively, were assessed in parallel. Giles et al recently found that spores do not require opsonization for phagocytosis (15). Our findings confirm their conclusions, and phagocytosis of unopsonized C. neoformans spores was clearly observed under our experimental conditions (see Movie S1 in the supplemental material), with the first phagocytosis events being detected by 55 min postincubation.…”

Section: Vol 77 2009supporting

confidence: 80%

See 1 more Smart Citation

Spores as Infectious Propagules ofCryptococcus neoformans

Velagapudi¹,

Hsueh²,

et al. 2009

View full text Add to dashboard Cite

Cryptococcus neoformans and Cryptococcus gattii are closely related pathogenic fungi that cause pneumonia and meningitis in both immunocompromised and immunocompetent hosts and are a significant global infectious disease risk. Both species are found in the environment and are acquired via inhalation, leading to an initial pulmonary infection. The infectious propagule is unknown but is hypothesized to be small desiccated yeast cells or spores produced by sexual reproduction (opposite-or same-sex mating). Here we characterize the morphology, germination properties, and virulence of spores. A comparative morphological analysis of hyphae and spores produced by opposite-sex mating, same-sex mating, and self-fertile diploid strains was conducted by scanning electron microscopy, yielding insight into hyphal/basidial morphology and spore size, structure, and surface properties. Spores isolated by microdissection were found to readily germinate even on water agarose medium. Thus, nutritional signals do not appear to be required to stimulate spore germination, and as-yet-unknown environmental factors may normally constrain germination in nature. As few as 500 CFU of a spore-enriched infectious inoculum (ϳ95% spores) of serotype A C. neoformans var. grubii were fully virulent (100% lethal infection) in both a murine inhalation virulence model and the invertebrate model host Galleria mellonella. In contrast to a previous report on C. neoformans var. neoformans, spores of C. neoformans var. grubii were not more infectious than yeast cells. Molecular analysis of isolates recovered from tissues of infected mice (lung, spleen, and brain) provides evidence for infection and dissemination by recombinant spore products. These studies provide a detailed morphological and physiological analysis of the spore and document that spores can serve as infectious propagules.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Vol 77 2009supporting

confidence: 80%

Spores as Infectious Propagules ofCryptococcus neoformans

Velagapudi¹,

Hsueh²,

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Gat1 negatively regulates mating in both mating-type a and a strains: During nitrogen limiting or starvation conditions, C. neoformans can undergo sexual reproduction that leads to the production of potentially infectious air-borne basidiospores (Kwon-Chung 1976; Lengeler et al 2000;Giles et al 2009). To address whether Gat1 plays a role in this sexual development, we created a gat1D derivative of MATa C. neoformans strain KN99a (VNI) by replacing the GAT1 ORF with the nourseothricin acetyl-transferase (NAT ) selectable marker, to serve as a mating partner for our existing gat1::NEO of MATa strain H99.…”

Section: Resultsmentioning

confidence: 99%

Nitrogen Metabolite Repression of Metabolism and Virulence in the Human Fungal Pathogen Cryptococcus neoformans

et al. 2011

View full text Add to dashboard Cite

Proper regulation of metabolism is essential to maximizing fitness of organisms in their chosen environmental niche. Nitrogen metabolite repression is an example of a regulatory mechanism in fungi that enables preferential utilization of easily assimilated nitrogen sources, such as ammonium, to conserve resources. Here we provide genetic, transcriptional, and phenotypic evidence of nitrogen metabolite repression in the human pathogen Cryptococcus neoformans. In addition to loss of transcriptional activation of catabolic enzyme-encoding genes of the uric acid and proline assimilation pathways in the presence of ammonium, nitrogen metabolite repression also regulates the production of the virulence determinants capsule and melanin. Since GATA transcription factors are known to play a key role in nitrogen metabolite repression, bioinformatic analyses of the C. neoformans genome were undertaken and seven predicted GATA-type genes were identified. A screen of these deletion mutants revealed GAT1, encoding the only global transcription factor essential for utilization of a wide range of nitrogen sources, including uric acid, urea, and creatinine-three predominant nitrogen constituents found in the C. neoformans ecological niche. In addition to its evolutionarily conserved role in mediating nitrogen metabolite repression and controlling the expression of catabolic enzyme and permease-encoding genes, Gat1 also negatively regulates virulence traits, including infectious basidiospore production, melanin formation, and growth at high body temperature (39°-40°). Conversely, Gat1 positively regulates capsule production. A murine inhalation model of cryptococcosis revealed that the gat1D mutant is slightly more virulent than wild type, indicating that Gat1 plays a complex regulatory role during infection.

show abstract

“…By definition, a basidiomycete fungus (e.g., Cryptococcus neoformans) produces hyphal structures during sexual differentiation that distinguish it from ascomycetes (Kwon-Chung 1975, 1976. Spores produced by Cryptococcus hyphae are quite infectious and may be the primary particle inhaled during a natural infection (Giles et al 2009;Velagapudi et al 2009). Therefore, the transition to hyphal growth that supports sporulation is required for the wide dissemination of Cryptococcus in the environment, as well as for infection of its mammalian hosts.…”

Section: Yeast Morphogenesis In a Basidiomycetementioning

confidence: 99%

Fungal Morphogenesis

Lin

Alspaugh

Liu

et al. 2014

Cold Spring Harbor Perspectives in Medicine

View full text Add to dashboard Cite

Morphogenesis in fungi is often induced by extracellular factors and executed by fungal genetic factors. Cell surface changes and alterations of the microenvironment often accompany morphogenetic changes in fungi. In this review, we will first discuss the general traits of yeast and hyphal morphotypes and how morphogenesis affects development and adaptation by fungi to their native niches, including host niches. Then we will focus on the molecular machinery responsible for the two most fundamental growth forms, yeast and hyphae. Last, we will describe how fungi incorporate exogenous environmental and host signals together with genetic factors to determine their morphotype and how morphogenesis, in turn, shapes the fungal microenvironment. PROPERTIES OF MORPHOGENESIS IN FUNGAL CELLS

show abstract

Elucidating the Pathogenesis of Spores from the Human Fungal PathogenCryptococcus neoformans

Cited by 177 publications

References 46 publications

Spores as Infectious Propagules ofCryptococcus neoformans

Spores as Infectious Propagules ofCryptococcus neoformans

Nitrogen Metabolite Repression of Metabolism and Virulence in the Human Fungal Pathogen Cryptococcus neoformans

Fungal Morphogenesis

Contact Info

Product

Resources

About