ArticleMolecular microbiology2012
A defect in ATP-citrate lyase links acetyl-CoA production, virulence factor elaboration and virulence in Cryptococcus neoformans.
Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 34 citations in OpenAlex.
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- Nitrogen limitation causes a seismic shift in redox state and phosphorylation of proteins implicated in carbon flux and lipidome remodeling in Rhodotorula toruloides.Biotechnology for biofuels and bioproducts · 2025Article
- Targeting fungal lipid synthesis for antifungal drug development and potentiation of contemporary antifungals.npj antimicrobials and resistance · 2025Review
- The role of ATP citrate lyase, phosphoketolase, and malic enzyme in oleaginous Rhodotorula toruloides.Applied microbiology and biotechnology · 2025Article
- Loss of the putative Rab GTPase, Ypt7, impairs the virulence ofFrontiers in microbiology · 2024Article
- A Limited Number of Amino Acid Permeases Are Crucial forInternational journal of microbiology · 2024Review
- The Response ofJournal of fungi (Basel, Switzerland) · 2023Article
- Article
- Vam6/Vps39/TRAP1-domain proteins influence vacuolar morphology, iron acquisition and virulence in Cryptococcus neoformans.Cellular microbiology · 2021Article
- Citrate-Mediated Acyl-CoA Synthesis Is Required for the Promotion of Growth and Triacylglycerol Production in Oleaginous YeastMicroorganisms · 2021Article
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- Editorial: Cellular and Molecular Mechanisms ofFrontiers in cellular and infection microbiology · 2019Article
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- CitE Enzymes Are Essential forFrontiers in cellular and infection microbiology · 2018Article
- Identification and Initial Characterization of the Effectors of an Anther Smut Fungus and Potential Host Target Proteins.International journal of molecular sciences · 2017Article
- Physiological Differences in Cryptococcus neoformans StrainsAntimicrobial agents and chemotherapy · 2017Review
- Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016Article
- Pyruvate Oxidase as a Critical Link between Metabolism and Capsule Biosynthesis in Streptococcus pneumoniae.PLoS pathogens · 2016Article
- Antitumor/Antifungal Celecoxib Derivative AR-12 is a Non-Nucleoside Inhibitor of the ANL-Family Adenylating Enzyme Acetyl CoA Synthetase.ACS infectious diseases · 2016Article
- In Vitro Analysis of Metabolites Secreted during Infection of Lung Epithelial Cells by Cryptococcus neoformans.PloS one · 2016Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The interaction of Cryptococcus neoformans with phagocytic cells of the innate immune system is a key step in disseminated disease leading to meningoencephalitis in immunocompromised individuals. Transcriptional profiling of cryptococcal cells harvested from cell culture medium or from macrophages found differential expression of metabolic and other functions during fungal adaptation to the intracellular environment. We focused on the ACL1 gene for ATP-citrate lyase, which converts citrate to acetyl-CoA, because this gene showed elevated transcript levels in macrophages and because of the importance of acetyl-CoA as a central metabolite. Mutants lacking ACL1 showed delayed growth on medium containing glucose, reduced cellular levels of acetyl-CoA, defective production of virulence factors, increased susceptibility to the antifungal drug fluconazole and decreased survival within macrophages. Importantly, acl1 mutants were unable to cause disease in a murine inhalation model, a phenotype that was more extreme than other mutants with defects in acetyl-CoA production (e.g. an acetyl-CoA synthetase mutant). Loss of virulence is likely due to perturbation of critical physiological interconnections between virulence factor expression and metabolism in C. neoformans. Phylogenetic analysis and structural modelling of cryptococcal Acl1 identified three indels unique to fungal protein sequences; these differences may provide opportunities for the development of pathogen-specific inhibitors.
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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.