Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 116, Issue 6, Pages 1651-1659Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI27890
Keywords
-
Categories
Funding
- NCRR NIH HHS [RR17677, C06 RR015455, P20 RR017677] Funding Source: Medline
- NIAID NIH HHS [AI56168, R01 AI056168] Funding Source: Medline
- NIGMS NIH HHS [U54 GM069338, GM069338] Funding Source: Medline
Ask authors/readers for more resources
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 (G1cCer), 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 G1cCer as a key virulence factor of cryptococcal pathogenicity, with important implications for future development of new antifungal strategies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available