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Updated: Feb 19, 2026

Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
11:07

Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans

Published on: December 19, 2014

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Cryptococcal dissemination to the central nervous system requires the vacuolar calcium transporter Pmc1

Eamim D Squizani1, Natália K Oliveira1, Júlia C V Reuwsaat1

  • 1Centro de Biotecnologia, UFRGS, Porto Alegre, RS, Brazil.

Cellular Microbiology
|November 8, 2017
PubMed

Insights

The calcium transporter Pmc1 is crucial for Cryptococcus neoformans to infect the central nervous system. Its absence impairs fungal survival and transmigration, highlighting Pmc1

Area of Science:

  • Mycology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Cryptococcus neoformans causes life-threatening meningoencephalitis in immunocompromised individuals, particularly HIV/AIDS patients.
  • Fungal transmigration across the blood-brain barrier is essential for central nervous system infection.
  • Virulence factors like urease are implicated in Cryptococcus neoformans' ability to breach the blood-brain barrier.

Purpose of the Study:

  • To investigate the role of the calcium transporter Pmc1 in Cryptococcus neoformans central nervous system infection.
  • To elucidate the molecular mechanisms underlying Pmc1-mediated fungal transmigration and virulence.

Main Methods:

  • Utilized a murine systemic infection model to assess the infectivity and survival of pmc1 null mutants.
  • Performed global gene expression profiling of the pmc1 mutant strain.
  • Assayed urease activity in calcium transporter null mutants.
  • Investigated the role of the transcription factor Crz1 and the Ca2+-calcineurin pathway.

Main Results:

  • The pmc1 null mutant exhibited impaired ability to infect and survive within the murine brain parenchyma.
  • Global expression profiling revealed differential expression of genes related to urease, capsule assembly, and the Ca2+-calcineurin pathway in the pmc1 mutant.
  • A significant decrease in urease activity was observed in calcium transporter null mutants.
  • The transcription factor Crz1 was found to regulate urease activity, and the Ca2+-calcineurin pathway positively controls genes involved in transmigration.

Conclusions:

  • The calcium transporter Pmc1 is essential for Cryptococcus neoformans to penetrate the central nervous system.
  • Pmc1 influences fungal virulence by modulating urease activity and potentially other transmigration factors.
  • The Ca2+-calcineurin-Crz1 signaling pathway plays a critical role in regulating fungal transmigration and virulence gene expression.
Keywords:
Cryptococcus neoformanscalcineurin signallingcalcium transportfungal virulencetransmigration

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