ArticleThe Journal of clinical investigation2010
Real-time imaging of trapping and urease-dependent transmigration of Cryptococcus neoformans in mouse brain.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers.
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139 citing papers in PubMed, 215 citations in OpenAlex.
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- Fungal expression strategies for heterologous production of antimicrobial peptides.Fungal biology and biotechnology · 2026Review
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- PDE4B deficiency aids macrophage differentiation and contributes to Cryptococcus neoformans brain infection.PLoS pathogens · 2026Article
- Microglia sense fungal infections through capsular components from capillary-bound Cryptococcus neoformans via endothelial nucleotide signaling.PLoS biology · 2026Article
- The Pain Is in the Brain With the Sugar-Coated Killer.The Journal of infectious diseases · 2025Review
- Reconsidering the blood-brain barrier: histopathology and microanatomy of cryptococcal CNS infection.Microbiology and molecular biology reviews : MMBR · 2025Review
- Calcium transport systems as virulence determinants: Mechanistic insights into fungal pathogenicity and antifungal resistance.Virulence · 2025Review
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- Neuroinflammation in fungal infections: from pathogen recognition to pathological manifestations.Disease models & mechanisms · 2025Review
- Virulence factors released by extracellular vesicles fromFrontiers in cellular and infection microbiology · 2025Review
- Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence ofJournal of fungi (Basel, Switzerland) · 2024Article
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- Mechanisms and Virulence Factors ofJournal of fungi (Basel, Switzerland) · 2024Review
- A Retrospective Analysis of Central and Peripheral Metabolic Characteristics in Patients with Cryptococcal Meningitis.Neurology and therapy · 2024Article
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- Measuring Urease and Phospholipase Secretion in Cryptococcus neoformans.Methods in molecular biology (Clifton, N.J.) · 2024Article
- The pathways and the mechanisms by whichMycology · 2024Review
- A multi-arm, parallel, preclinical study investigating the potential benefits of acetazolamide, candesartan, and triciribine in combination with fluconazole for the treatment of cryptococcal meningoencephalitis.European journal of pharmacology · 2023Article
79 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infectious meningitis and encephalitis is caused by invasion of circulating pathogens into the brain. It is unknown how the circulating pathogens dynamically interact with brain endothelium under shear stress, leading to invasion into the brain. Here, using intravital microscopy, we have shown that Cryptococcus neoformans, a yeast pathogen that causes meningoencephalitis, stops suddenly in mouse brain capillaries of a similar or smaller diameter than the organism, in the same manner and with the same kinetics as polystyrene microspheres, without rolling and tethering to the endothelial surface. Trapping of the yeast pathogen in the mouse brain was not affected by viability or known virulence factors. After stopping in the brain, C. neoformans was seen to cross the capillary wall in real time. In contrast to trapping, viability, but not replication, was essential for the organism to cross the brain microvasculature. Using a knockout strain of C. neoformans, we demonstrated that transmigration into the mouse brain is urease dependent. To determine whether this could be amenable to therapy, we used the urease inhibitor flurofamide. Flurofamide ameliorated infection of the mouse brain by reducing transmigration into the brain. Together, these results suggest that C. neoformans is mechanically trapped in the brain capillary, which may not be amenable to pharmacotherapy, but actively transmigrates to the brain parenchyma with contributions from urease, suggesting that a therapeutic strategy aimed at inhibiting this enzyme could help prevent meningitis and encephalitis caused by C. neoformans infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.