Aging as an emergent factor that contributes to phenotypic variation in Cryptococcus neoformans

Bouklas, Tejas; Fries, Bettina C.

doi:10.1016/j.fgb.2014.10.004

Cited by 14 publications

(8 citation statements)

References 74 publications

(100 reference statements)

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“…For example, the age of individual cryptococcal cells has emerged as a factor that affects survival in the host and subsequent pathogenesis 25 . Older cells present in the initial infection, referred to as cells, are better able to resist phagocytosis and killing by phagocytes and are resistant to antifungal drugs.…”

Section: Cryptococcal Pathogenesismentioning

confidence: 99%

Cryptococcus: from environmental saprophyte to global pathogen

et al. 2015

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Cryptococcosis is a globally distributed invasive fungal infection that is caused by species within the genus Cryptococcus which presents substantial therapeutic challenges. Although natural human-to-human transmission has never been observed, recent work has identified multiple virulence mechanisms that enable cryptococci to infect, disseminate within and ultimately kill their human host. In this Review, we describe these recent discoveries that illustrate the intricacy of host-pathogen interactions and reveal new details about the host immune responses that either help to protect against disease or increase host susceptibility. In addition, we discuss how this improved understanding of both the host and the pathogen informs potential new avenues for therapeutic development.

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Section: Cryptococcal Pathogenesismentioning

confidence: 99%

Cryptococcus: from environmental saprophyte to global pathogen

et al. 2015

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“…Notably, cell aging and nutrient deprivation have each been linked to pathogenesis in C. neoformans. First, cells that have undergone many replicative cycles and are thus older generationally have been shown to accumulate during chronic cryptococcal infections and manifest distinct phenotypic traits associated with virulence (66,67). For example, these cells display a large body size and thicker cell wall, both of which have been correlated with increased drug resistance and decreased susceptibility to killing by macrophages.…”

Section: Discussionmentioning

confidence: 99%

Solid-state NMR spectroscopy identifies three classes of lipids inC. neoformansmelanized cell walls and whole fungal cells

Chrissian

Camacho

Kelly

et al. 2020

Preprint

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A primary virulence-associated trait of the opportunistic fungal pathogen Cryptococcus neoformans is the production of melanin pigments that are deposited into the cell wall and interfere with the host immune response. Previously, our solid-state NMR studies of isolated melanized cell walls (melanin ‘ghosts’) revealed that the pigments are strongly associated with lipids, but their identities, origins, and potential roles were undetermined. Herein, we exploited spectral editing techniques to identify and quantify the lipid molecules associated with pigments in melanin ghosts. The lipid profiles were remarkably similar in whole C. neoformans cells, grown under either melanizing or non-melanizing conditions; triglycerides (TGs), sterol esters (SEs) and polyisoprenoids (PPs) were the major constituents. Although no quantitative differences were found between melanized and non-melanized cells, melanin ghosts were relatively enriched in SEs and PPs. In contrast to lipid structures reported during early stages of fungal growth in nutrient-rich media, variants found herein could be linked to nutrient stress, cell aging, and subsequent production of substances that promote chronic fungal infections. The fact that TGs and SEs are the typical cargo of lipid droplets suggests that these organelles could be connected to C. neoformans melanin synthesis. Moreover, the discovery of PPs is intriguing because dolichol is a well-established constituent of human neuromelanin. The presence of these lipid species even in non-melanized cells suggests that they could be produced constitutively under stress conditions in anticipation of melanin synthesis. These findings demonstrate that C. neoformans lipids are more varied compositionally and functionally than previously recognized.

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“…The aging of C. neoformans cells within the lungs is a source of phenotypic variation that potentially enhances extrapulmonary dissemination [ 99 ]. C. neoformans aging can be categorized as chronological aging or replicative aging.…”

Section: Examples Of Fungal Factors Influencing Pulmonary Escapementioning

confidence: 99%

Mechanisms of Pulmonary Escape and Dissemination by Cryptococcus neoformans

Denham

Brown

2018

JoF

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Cryptococcus neoformans is a common environmental saprophyte and human fungal pathogen that primarily causes disease in immunocompromised individuals. Similar to many environmentally acquired human fungal pathogens, C. neoformans initiates infection in the lungs. However, the main driver of mortality is invasive cryptococcosis leading to fungal meningitis. After C. neoformans gains a foothold in the lungs, a critical early step in invasion is transversal of the respiratory epithelium. In this review, we summarize current knowledge relating to pulmonary escape. We focus on fungal factors that allow C. neoformans to disseminate from the lungs via intracellular and extracellular routes.

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Aging as an emergent factor that contributes to phenotypic variation in Cryptococcus neoformans

Cited by 14 publications

References 74 publications

Cryptococcus: from environmental saprophyte to global pathogen

Cryptococcus: from environmental saprophyte to global pathogen

Solid-state NMR spectroscopy identifies three classes of lipids inC. neoformansmelanized cell walls and whole fungal cells

Mechanisms of Pulmonary Escape and Dissemination by Cryptococcus neoformans

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