ArticleInfection and immunity2010
Survival defects of Cryptococcus neoformans mutants exposed to human cerebrospinal fluid result in attenuated virulence in an experimental model of meningitis.
Article in Infection and immunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 53 citations in OpenAlex.
- Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis.The Journal of clinical investigation · 2014Trial
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- The protein phosphatase 2C domain contributes to the pathobiological function of adenylyl cyclase inbioRxiv : the preprint server for biology · 2025Article
- Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025Review
- Models for Inducing Experimental Cryptococcosis in Mice.Methods in molecular biology (Clifton, N.J.) · 2024Article
- The Rabbit Model of Cryptococcal Meningitis.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- Vam6/Vps39/TRAP1-domain proteins influence vacuolar morphology, iron acquisition and virulence in Cryptococcus neoformans.Cellular microbiology · 2021Article
- Assessing the virulence of Cryptococcus neoformans causing meningitis in HIV infected and uninfected patients in Vietnam.Medical mycology · 2020Article
- It's not all about us: evolution and maintenance of Cryptococcus virulence requires selection outside the human host.Yeast (Chichester, England) · 2017Article
- Article
- Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans.Nature communications · 2016Article
- Systemic Approach to Virulence Gene Network Analysis for Gaining New Insight into Cryptococcal Virulence.Frontiers in microbiology · 2016Article
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- Cryptococcosis diagnosis and treatment: What do we know now.Fungal genetics and biology : FG & B · 2015Review
- Cryptococcus inositol utilization modulates the host protective immune response during brain infection.Cell communication and signaling : CCS · 2014Article
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- Article
- The Cryptococcus neoformans Rim101 transcription factor directly regulates genes required for adaptation to the host.Molecular and cellular biology · 2014Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cryptococcus neoformans is a fungal pathogen that encounters various microenvironments during growth in the mammalian host, including intracellular vacuoles, blood, and cerebrospinal fluid (CSF). Because the CSF is isolated by the blood-brain barrier, we hypothesize that CSF presents unique stresses that C. neoformans must overcome to establish an infection. We assayed 1,201 mutants for survival defects in growth media, saline, and human CSF. We assessed CSF-specific mutants for (i) mutant survival in both human bronchoalveolar lavage (BAL) fluid and fetal bovine serum (FBS), (ii) survival in macrophages, and (iii) virulence using both Caenorhabditis elegans and rabbit models of cryptococcosis. Thirteen mutants exhibited significant survival defects unique to CSF. The mutations of three of these mutants were recreated in the clinical serotype A strain H99: deletions of the genes for a cation ATPase transporter (ena1Δ), a putative NEDD8 ubiquitin-like protein (rub1Δ), and a phosphatidylinositol 4-kinase (pik1Δ). Mutant survival rates in yeast media, saline, and BAL fluid were similar to those of the wild type; however, survival in FBS was reduced but not to the levels in CSF. These mutant strains also exhibited decreased intracellular survival in macrophages, various degrees of virulence in nematodes, and severe attenuation of survival in a rabbit meningitis model. We analyzed the CSF by mass spectrometry for candidate compounds responsible for the survival defect. Our findings indicate that the genes required for C. neoformans survival in CSF ex vivo are necessary for survival and infection in this unique host environment.
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