<i>Variability</i>
            of Phenotypic Traits in
            <i>Cryptococcus</i>
            Varieties and Species and the Resulting Implications for Pathogenesis

Gupta, Garima; Fries, Bettina C.

doi:10.2217/fmb.10.44

Cited by 16 publications

(21 citation statements)

References 164 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microevolution and phenotypic variability of C. neoformans isolates occurs in the laboratory through multiple in vitro passages (reviewed by [42]–[44]). Therefore, an important factor considered in our experimental design when testing clinical isolates was the use of colonies isolated directly from CSF.…”

Section: Resultsmentioning

confidence: 99%

Deletion of Cryptococcus neoformans AIF Ortholog Promotes Chromosome Aneuploidy and Fluconazole-Resistance in a Metacaspase-Independent Manner

et al. 2011

View full text Add to dashboard Cite

Apoptosis is a form of programmed cell death critical for development and homeostasis in multicellular organisms. Apoptosis-like cell death (ALCD) has been described in several fungi, including the opportunistic human pathogen Cryptococcus neoformans. In addition, capsular polysaccharides of C. neoformans are known to induce apoptosis in host immune cells, thereby contributing to its virulence. Our goals were to characterize the apoptotic signaling cascade in C. neoformans as well as its unique features compared to the host machinery to exploit the endogenous fungal apoptotic pathways as a novel antifungal strategy in the future. The dissection of apoptotic pathways revealed that apoptosis-inducing factor (Aif1) and metacaspases (Mca1 and Mca2) are independently required for ALCD in C. neoformans. We show that the apoptotic pathways are required for cell fusion and sporulation during mating, indicating that apoptosis may occur during sexual development. Previous studies showed that antifungal drugs induce ALCD in fungi and that C. neoformans adapts to high concentrations of the antifungal fluconazole (FLC) by acquisition of aneuploidy, especially duplication of chromosome 1 (Chr1). Disruption of aif1, but not the metacaspases, stimulates the emergence of aneuploid subpopulations with Chr1 disomy that are resistant to fluconazole (FLCR) in vitro and in vivo. FLCR isolates in the aif1 background are stable in the absence of the drug, while those in the wild-type background readily revert to FLC sensitivity. We propose that apoptosis orchestrated by Aif1 might eliminate aneuploid cells from the population and defects in this pathway contribute to the selection of aneuploid FLCR subpopulations during treatment. Aneuploid clinical isolates with disomies for chromosomes other than Chr1 exhibit reduced AIF1 expression, suggesting that inactivation of Aif1 might be a novel aneuploidy-tolerating mechanism in fungi that facilitates the selection of antifungal drug resistance.

show abstract

Section: Resultsmentioning

confidence: 99%

Deletion of Cryptococcus neoformans AIF Ortholog Promotes Chromosome Aneuploidy and Fluconazole-Resistance in a Metacaspase-Independent Manner

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Several studies have demonstrated that during chronic infection with C. neoformans , phenotypic variants emerge [10–14]. Such ‘microevolution’ has been documented in serial isolates [15,16] and experimental murine infection [17].…”

Section: Capsule Induction Is a Major Determinant Of Phenotypic Variamentioning

confidence: 99%

Aging: An Emergent Phenotypic Trait that Contributes to the Virulence of Cryptococcus Neoformans

Bouklas

Fries

2015

Future Microbiol.

View full text Add to dashboard Cite

The pathogenic fungus, Cryptococcus neoformans, is known to undergo phenotypic variation, which affects its virulence in the host. Recent investigations on C. neoformans cells in humans have validated the concept that phenotypic variation is present and relevant for the outcome of chronic cryptococcosis. The C. neoformans capsule is not the only trait that varies among strains. An emerging variant is the “old cell phenotype” generated when C. neoformans undergoes replicative aging. This phenotype, which other than larger size also exhibits a thickened cell wall, inhibits phagocytosis and killing by antifungals in vitro. In concert with the finding that old cells accumulate in vivo, this emergent trait could have significant impact on cryptococcal virulence and infection, and contribute to treatment failure.

show abstract

“…It includes at least 37 different species, of which two species namely, C.neoformans and C.gattii are recognized as important human and animal pathogens [17,18]. Rarely, other species of Cryptoccoccus such as C.albidus and C.laurentii are also reported to be of medical significance [9].…”

Section: Etiological Agentsmentioning

confidence: 99%

Cryptococcosis: An Emerging Airborne Mycosis of Global Concern

Dave¹

2016

Air Water Borne Diseases

View full text Add to dashboard Cite

Cryptococcosis, an emerging highly infectious respiratory mycosis, is mainly caused by Cryptococcus neoformans and Cryptococcus gattii, which exist as saprobe in the environment. Currently, nine molecular types, five in C.neoformans and four in C. gattii are identified. The disease occurs in sporadic and epidemic form resulting into significant morbidity and mortality, especially in immunocompromised patients. Globally, cryptococcosis causes about 625,000 deaths annually. The clinical manifestation of pulmonary cryptococcosis includes cough, weight loss, sputum, chest pain, dysponea, fever, headache, and hemoptysis. The demonstration of pathogen both by direct microscopy in India ink and its isolation on Pal sunflower seed medium is still considered as gold standard to confirm an unequivocal diagnosis of cryptococcosis. The morphology of isolates can be easily studied in "Narayan" stain. The fluconazole, being a less toxic drug, is recommended for the management of pulmonary cryptococcosis. It is emphasized to undertake molecular characterization of Cryptococcus isolates to know the genotypes prevalent in different regions of the world. Since many laboratory in poor resource countries do not have facilities to undertake biochemical test, it is therefore, advised to use easily available, very sensitive, highly specific and low cost "Pal sunflower seed medium" to make an early diagnosis to save the life of patients from this enigmatic mycosis. Further research work on pathogenesis, epidemiology, and chemotherapy may be rewarding.

show abstract

Variability of Phenotypic Traits in Cryptococcus Varieties and Species and the Resulting Implications for Pathogenesis

Cited by 16 publications

References 164 publications

Deletion of Cryptococcus neoformans AIF Ortholog Promotes Chromosome Aneuploidy and Fluconazole-Resistance in a Metacaspase-Independent Manner

Deletion of Cryptococcus neoformans AIF Ortholog Promotes Chromosome Aneuploidy and Fluconazole-Resistance in a Metacaspase-Independent Manner

Aging: An Emergent Phenotypic Trait that Contributes to the Virulence of Cryptococcus Neoformans

Cryptococcosis: An Emerging Airborne Mycosis of Global Concern

Contact Info

Product

Resources

About