Browsing by Author "Nielsen, Kirsten"

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    ATI-2307 Exhibits Equivalent Antifungal Activity in Cryptococcus neoformans Clinical Isolates With High and Low Fluconazole IC50
    (Frontiers in Cellular and Infection Microbiology, 11, 695240., 2021-06-23) Gerlach, Elliot S.; Luggya, Tony S.; Akampurira, Andrew; Rhein, Joshua; Nielsen, Kirsten
    Half maximal inhibitory concentrations (IC50) to the experimental drug ATI-2307 and complete inhibition (IC90) of the common clinically used antifungal drug amphotericin B were determined by microbroth dilution assay for a collection of 69 clinical isolates of Cryptococcus neoformans from Uganda that had high fluconazole IC50 values. The majority of the clinical isolates tested had fluconazole IC50 at or above 8 µg/mL, but were susceptible to both amphotericin B (IC90 ≤1 μg/mL) and ATI-2307 (IC50 ≤0.0312 µg/mL). No correlation between increased fluconazole minimum inhibitory concentration (MIC) and ATI-2307 or amphotericin B MIC was observed, suggesting that the cellular changes impacting fluconazole susceptibility did not impact the effectiveness of ATI-2307. Our results suggest that ATI-2307 is a promising new antifungal drug for use in the context of high fluconazole or other antifungal drug MICs and/or in combination drug therapy regimens.
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    MinION Whole‑Genome Sequencing in Resource‑Limited Settings: Challenges and Opportunities
    (Current Clinical Microbiology Reports, 2022-11-17) Wasswa, Fredrickson B.; Kassaza, Kennedy; Nielsen, Kirsten; Bazira, Joel
    The introduction of MinION whole-genome sequencing technology greatly increased and simplified complete genome sequencing in various fields of science across the globe. Sequences have been generated from complex organisms to microorganisms and are stored in genome databases that are readily accessible by researchers. Various new software for genome analysis, along with upgrades to older software packages, are being generated. New protocols are also being validated that enable WGS technology to be rapidly and increasingly used for sequencing in field settings. MinION WGS technology has been implemented in developed countries due to its advantages: portability, real-time analysis, and lower cost compared to other sequencing technologies. While these same advantages are critical in developing countries, MinION WGS technology is still under-utilized in resource-limited settings. In this review, we look at the applications, advantages, challenges, and opportunities of using MinION WGS in resource-limited settings.
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    Pulmonary granuloma formation during latent Cryptococcus neoformans infection in C3HeB/FeJ mice involves progression through three immunological phases
    (mBio, 2025-01-01) Betancourt, Jovany J.; Mutyaba, Issa; Meya, David B.; Nielsen, Kirsten
    Cryptococcus neoformans is a fungal pathogen that can cause lethal disease in immunocompromised patients. Immunocompetent host immune responses, such as formation of pulmonary granulomas, control the infection and prevent disseminated disease. Little is known about the immunological conditions establishing the latent infection granuloma in the lungs. To investigate this, we performed an analysis of pulmonary immune cell populations, cytokine changes, and granuloma formation during infection with a latent disease-causing clinical isolate in C3HeB/FeJ mice over 360 days. We found that latently infected mice progress through three phases of granuloma formation where different immune profiles dominate: an early phase characterized by eosinophilia, high IL-4/IL-13, and C. neoformans proliferation in the lungs; an intermediate phase characterized by multinucleated giant cell formation, high IL-1α/IFNγ, granuloma expansion, and increased blood antigen levels; and a late phase characterized by a significant expansion of T cells, granuloma condensation, and decreases in lung fungal burden and blood antigen levels. These findings highlight a complex series of immune changes that occur during the establishment of granulomas that control C. neoformans in the lungs and lay the foundation for studies to identify critical beneficial immune responses to Cryptococcus infections.