ArticleInfection and immunity2014
Defects in phosphate acquisition and storage influence virulence of Cryptococcus neoformans.
Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
51 citing papers in PubMed, 66 citations in OpenAlex.
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- Investigation of human leukocyte antigen alleles as risk factors for cryptococcal disease in Ugandan individuals with HIV.Human immunology · 2026Article
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- Plants, fungi, and antifungals: A little less talk, a little more action.PLoS pathogens · 2025Article
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- Polyphosphatases have a polyphosphate-independent influence on the virulence ofInfection and immunity · 2025Article
- Cryptococcal nutrient acquisition and pathogenesis: dining on the host.Microbiology and molecular biology reviews : MMBR · 2025Review
- Herbicides as fungicides: Targeting heme biosynthesis in the maize pathogen Ustilago maydis.Molecular plant pathology · 2024Article
- Candida albicans' inorganic phosphate transport and evolutionary adaptation to phosphate scarcity.PLoS genetics · 2024Article
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- Phosphate availability conditions caspofungin tolerance, capsule attachment and titan cell formation inFrontiers in fungal biology · 2024Article
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- Phosphate accumulation in rice leaves promotes fungal pathogenicity and represses host immune responses during pathogen infection.Frontiers in plant science · 2023Article
- Interaction of calcium responsive proteins and transcriptional factors with the PHO regulon in yeasts and fungi.Frontiers in cell and developmental biology · 2023Review
- A dissemination-prone morphotype enhances extrapulmonary organ entry by Cryptococcus neoformans.Cell host & microbe · 2022Article
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- The phosphate language of fungi.Trends in microbiology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Nutrient acquisition and sensing are critical aspects of microbial pathogenesis. Previous transcriptional profiling indicated that the fungal pathogen Cryptococcus neoformans, which causes meningoencephalitis in immunocompromised individuals, encounters phosphate limitation during proliferation in phagocytic cells. We therefore tested the hypothesis that phosphate acquisition and polyphosphate metabolism are important for cryptococcal virulence. Deletion of the high-affinity uptake system interfered with growth on low-phosphate medium, perturbed the formation of virulence factors (capsule and melanin), reduced survival in macrophages, and attenuated virulence in a mouse model of cryptococcosis. Additionally, analysis of nutrient sensing functions for C. neoformans revealed regulatory connections between phosphate acquisition and storage and the iron regulator Cir1, cyclic AMP (cAMP)-dependent protein kinase A (PKA), and the calcium-calmodulin-activated protein phosphatase calcineurin. Deletion of the VTC4 gene encoding a polyphosphate polymerase blocked the ability of C. neoformans to produce polyphosphate. The vtc4 mutant behaved like the wild-type strain in interactions with macrophages and in the mouse infection model. However, the fungal load in the lungs was significantly increased in mice infected with vtc4 deletion mutants. In addition, the mutant was impaired in the ability to trigger blood coagulation in vitro, a trait associated with polyphosphate. Overall, this study reveals that phosphate uptake in C. neoformans is critical for virulence and that its regulation is integrated with key signaling pathways for nutrient sensing.
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Registered trials
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.