Unraveling Capsule Biosynthesis and Signaling Networks in Cryptococcus neoformans

Jang, Eun-Ha; Kim, Ji‐Seok; Yu, Seong-Ryong; Bahn, Yong-Sun

doi:10.1128/spectrum.02866-22

Cited by 14 publications

(17 citation statements)

References 41 publications

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“…1C). Furthermore, Jang et al found that Yap1 functions upstream of Gat201 during capsule induction (18). The consistent phenotypes observed across components of previously described regulatory pathways provides confidence that these genes are important for CO2 responses.…”

Section: Resultsmentioning

confidence: 63%

The fungal pathogen Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry

Krysan

Ristow

Jezewski

et al. 2023

Preprint

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Cryptococcus spp. are environmental fungi that first must adapt to the host environment before they can cause life-threatening meningitis in immunocompromised patients. Host CO2 concentrations are 100-fold higher than the external environment and strains unable to grow at host CO2 concentrations are not pathogenic. Using a genetic screening and transcriptional profiling approach, we found that the TOR pathway is critical for C. neoformans adaptation to host CO2 partly through Ypk1-dependent remodeling of phosphatidylserine asymmetry at the plasma membrane. We also identified a candidate C. neoformans floppase (Lat1) that is highly expressed in CO2-sensitive environmental strains and suppresses CO2-induced phosphatidylserine remodeling. Interestingly, regulation of plasma membrane lipid asymmetry by the TOR-Ypk1 axis is distinct in C. neoformans compared to S. cerevisiae. Finally, host CO2 concentrations suppress the C. neoformans pathways that respond to host temperature (Mpk1) and pH (Rim101), indicating that host adaptation requires a stringent balance among distinct stress responses.

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Section: Resultsmentioning

confidence: 63%

The fungal pathogen Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry

Krysan

Ristow

Jezewski

et al. 2023

Preprint

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“…Vishniacozyma victoraie stains differ in regard to the presence of absence of a capsule ( de Garcia et al., 2012 ). Examining the lack of a capsule formation by this yeast and the potential for capsule formation under certain conditions warrant future study ( Vitale et al., 2012 ; Jang et al., 2022 ). Lastly, three PBS-exposed mice were reported to have GMS + histiocyte granules.…”

Section: Discussionmentioning

confidence: 99%

Persisting Cryptococcus yeast species Vishniacozyma victoriae and Cryptococcus neoformans elicit unique airway inflammation in mice following repeated exposure

Rush

Blackwood²,

Lemons³

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundAllergic airway disease (AAD) is a growing concern in industrialized nations and can be influenced by fungal exposures. Basidiomycota yeast species such as Cryptococcus neoformans are known to exacerbate allergic airway disease; however, recent indoor assessments have identified other Basidiomycota yeasts, including Vishniacozyma victoriae (syn. Cryptococcus victoriae), to be prevalent and potentially associated with asthma. Until now, the murine pulmonary immune response to repeated V. victoriae exposure was previously unexplored.ObjectiveThis study aimed to compare the immunological impact of repeated pulmonary exposure to Cryptococcus yeasts.MethodsMice were repeatedly exposed to an immunogenic dose of C. neoformans or V. victoriae via oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and lungs were collected to examine airway remodeling, inflammation, mucous production, cellular influx, and cytokine responses at 1 day and 21 days post final exposure. The responses to C. neoformans and V. victoriae were analyzed and compared.ResultsFollowing repeated exposure, both C. neoformans and V. victoriae cells were still detectable in the lungs 21 days post final exposure. Repeated C. neoformans exposure initiated myeloid and lymphoid cellular infiltration into the lung that worsened over time, as well as an IL-4 and IL-5 response compared to PBS-exposed controls. In contrast, repeated V. victoriae exposure induced a strong CD4+ T cell-driven lymphoid response that started to resolve by 21 days post final exposure.DiscussionC. neoformans remained in the lungs and exacerbated the pulmonary immune responses as expected following repeated exposure. The persistence of V. victoriae in the lung and strong lymphoid response following repeated exposure were unexpected given its lack of reported involvement in AAD. Given the abundance in indoor environments and industrial utilization of V. victoriae, these results highlight the importance to investigate the impact of frequently detected fungal organisms on the pulmonary response following inhalational exposure. Moreover, it is important to continue to address the knowledge gap involving Basidiomycota yeasts and their impact on AAD.

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“…Notably, both of the benzoquinone carbonyl groups are likely to react with oxime or oxime ether. According to the spectral data of 1 H NMR, 13 C NMR, and HRMS, only one benzoquinone carbonyl group participated in the reaction. To further determine the absolute configuration of the target compound, X-Ray crystallographic analysis was performed (Figure 2B and Table S4 in the Supporting Information).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…1 H NMR (600 MHz, DMSO-d 6 , TMS): δ 8.18 (d, J = 5.1 Hz, 1H), 7.64 (d, J = 5.1 Hz, 1H), 4.34 (s, 3H), 2.55 (s, 3H). 13 2B and Table S4, respectively.…”

Section: Z)-8-(methoxyimino)-3-methylthieno[3′2':45]benzo[12-d]isoxaz...mentioning

confidence: 99%

Discovery of New Tricyclic Oxime Sampangine Derivatives as Potent Antifungal Agents for the Treatment of Cryptococcosis and Candidiasis

Yang,

Liu,

et al. 2024

J. Med. Chem.

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Cryptococcus neoformans (C. neoformans) and Candida albicans (C. albicans) are classified as the critical priority groups among the pathogenic fungi, highlighting the urgent need for developing more effective antifungal therapies. On the basis of antifungal natural product sampangine, herein, a series of tricyclic oxime and oxime ether derivatives were designed. Among them, compound WZ-2 showed excellent inhibitory activity against C. neoformans (MIC 80 = 0.016 μg/mL) and synergized with fluconazole to treat resistant C. albicans (FICI = 0.078). Interestingly, compound WZ-2 effectively inhibited virulence factors (e.g., capsule, biofilm, and yeast-to-hypha morphological transition), suggesting the potential to overcome drug resistance. In a mouse model of cryptococcal meningitis, compound WZ-2 (5 mg/kg) effectively reduced the brain C. neoformans H99 burden. Furthermore, compound WZ-2 alone and its combination with fluconazole also significantly reduced the kidney burden of the drugresistant strain (0304103) and sensitive strain (SC5314) of C. albicans.

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Unraveling Capsule Biosynthesis and Signaling Networks in Cryptococcus neoformans

Cited by 14 publications

References 41 publications

The fungal pathogen Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry

The fungal pathogen Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry

Persisting Cryptococcus yeast species Vishniacozyma victoriae and Cryptococcus neoformans elicit unique airway inflammation in mice following repeated exposure

Discovery of New Tricyclic Oxime Sampangine Derivatives as Potent Antifungal Agents for the Treatment of Cryptococcosis and Candidiasis

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