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Citations to this article

Glucosylceramide synthase is an essential regulator of pathogenicity of Cryptococcus neoformans
Philipp C. Rittershaus, … , Chiara Luberto, Maurizio Del Poeta
Philipp C. Rittershaus, … , Chiara Luberto, Maurizio Del Poeta
Published June 1, 2006
Citation Information: J Clin Invest. 2006;116(6):1651-1659. https://doi.org/10.1172/JCI27890.
View: Text | PDF | Corrigendum
Research Article Microbiology Article has an altmetric score of 10

Glucosylceramide synthase is an essential regulator of pathogenicity of Cryptococcus neoformans

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Abstract

The pathogenic fungus Cryptococcus neoformans infects humans upon inhalation and causes the most common fungal meningoencephalitis in immunocompromised subjects worldwide. In the host, C. neoformans is found both intracellularly and extracellularly, but how these two components contribute to the development of the disease is largely unknown. Here we show that the glycosphingolipid glucosylceramide (GlcCer), which is present in C. neoformans, was essential for fungal growth in host extracellular environments, such as in alveolar spaces and in the bloodstream, which are characterized by a neutral/alkaline pH, but not in the host intracellular environment, such as in the phagolysosome of macrophages, which is characteristically acidic. Indeed, a C. neoformans mutant strain lacking GlcCer did not grow in vitro at a neutral/alkaline pH, yet it had no growth defect at an acidic pH. The mechanism by which GlcCer regulates alkali tolerance was by allowing the transition of C. neoformans through the cell cycle. This study establishes C. neoformans GlcCer as a key virulence factor of cryptococcal pathogenicity, with important implications for future development of new antifungal strategies.

Authors

Philipp C. Rittershaus, Talar B. Kechichian, Jeremy C. Allegood, Alfred H. Merrill, Mirko Hennig, Chiara Luberto, Maurizio Del Poeta

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 Total
Citations: 3 7 5 3 15 14 6 9 5 12 12 8 4 4 15 7 5 7 4 2 147
Citation information
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Citations to this article in year 2013 (4)

Title and authors Publication Year
Uncoupling of mRNA synthesis and degradation impairs adaptation to host temperature in Cryptococcus neoformans: mRNA decay in cryptococcal temperature adaptation
AL Bloom, JT Solomons, VE Havel, JC Panepinto
Molecular Microbiology 2013
The Transcriptional Response of Cryptococcus neoformans to Ingestion by Acanthamoeba castellanii and Macrophages Provides Insights into the Evolutionary Adaptation to the Mammalian Host
L da S. Derengowski, HC Paes, P Albuquerque, AH Tavares, L Fernandes, I Silva-Pereira, A Casadevall
Eukaryotic cell 2013
Characterization of cell wall lipids from the pathogenic phase of Paracoccidioides brasiliensis cultivated in the presence or absence of human plasma
LV Longo, ES Nakayasu, F Gazos-Lopes, MC Vallejo, AL Matsuo, IC Almeida, R Puccia
PloS one 2013
Glucosylceramide transferase activity is critical for encystation and viable cyst production by an intestinal protozoan, Giardia lamblia
TL Mendez, AD Chatterjee, TT Duarte, F Gazos-Lopes, L Robles-Martinez, D Roy, J Sun, RA Maldonado, S Roychowdhury, IC Almeida, S Das
The Journal of biological chemistry 2013

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