ArticleEukaryotic cell2010
Fungal homoserine kinase (thr1Delta) mutants are attenuated in virulence and die rapidly upon threonine starvation and serum incubation.
Article in Eukaryotic cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence ofJournal of fungi (Basel, Switzerland) · 2024Article
- Molecular targets for antifungals in amino acid and protein biosynthetic pathways.Amino acids · 2021Review
- The Vacuolar Morphogenesis Protein Vam6-Like Protein Vlp1 Is Required for Pathogenicity ofJournal of fungi (Basel, Switzerland) · 2021Article
- Molecular Characterization ofFrontiers in microbiology · 2021Article
- More Than Just Cleaning: Ubiquitin-Mediated Proteolysis in Fungal Pathogenesis.Frontiers in cellular and infection microbiology · 2021Review
- A Predicted Mannoprotein Cmp1 Regulates Fungal Virulence inPathogens (Basel, Switzerland) · 2020Article
- Metabolic profiling of Candida clinical isolates of different species and infection sources.Scientific reports · 2020Article
- The regulation of the sulfur amino acid biosynthetic pathway in Cryptococcus neoformans: the relationship of Cys3, Calcineurin, and Gpp2 phosphatases.Scientific reports · 2019Article
- Article
- THR1 mediates GCN4 and CDC4 to link morphogenesis with nutrient sensing and the stress response in Candida albicans.International journal of molecular medicine · 2018Article
- Potential targets for the development of new antifungal drugs.The Journal of antibiotics · 2018Review
- Novel biosynthetic pathway for sulfur amino acids in Cryptococcus neoformans.Current genetics · 2018Article
- Genome-Wide Screen forG3 (Bethesda, Md.) · 2018Article
- Nutritional Requirements and Their Importance for Virulence of Pathogenic Cryptococcus Species.Microorganisms · 2017Review
- Article
- Inhibitors of amino acids biosynthesis as antifungal agents.Amino acids · 2015Review
- The Role of Amino Acid Permeases and Tryptophan Biosynthesis in Cryptococcus neoformans Survival.PloS one · 2015Article
- Homoserine and quorum-sensing acyl homoserine lactones as alternative sources of threonine: a potential role for homoserine kinase in insect-stage Trypanosoma brucei.Molecular microbiology · 2015Article
- The role of the de novo pyrimidine biosynthetic pathway in Cryptococcus neoformans high temperature growth and virulence.Fungal genetics and biology : FG & B · 2014Article
- Accumulation of a threonine biosynthetic intermediate attenuates general amino acid control by accelerating degradation of Gcn4 via Pho85 and Cdk8.PLoS genetics · 2014Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The fungally conserved subset of amino acid biosynthetic enzymes not present in humans offer exciting potential as an unexploited class of antifungal drug targets. Since threonine biosynthesis is essential in Cryptococcus neoformans, we further explored the potential of threonine biosynthetic enzymes as antifungal drug targets by determining the survival in mice of Saccharomyces cerevisiae homoserine kinase (thr1Delta) and threonine synthase (thr4Delta) mutants. In striking contrast to aspartate kinase (hom3Delta) mutants, S. cerevisiae thr1Delta and thr4Delta mutants were severely depleted after only 4 h in vivo. Similarly, Candida albicans thr1Delta mutants, but not hom3Delta mutants, were significantly attenuated in virulence. Consistent with the in vivo phenotypes, S. cerevisiae thr1Delta and thr4Delta mutants as well as C. albicans thr1Delta mutants were extremely serum sensitive. In both species, serum sensitivity was suppressed by the addition of threonine, a feedback inhibitor of Hom3p. Because mutation of the HOM3 and HOM6 genes, required for the production of the toxic pathway intermediate homoserine, also suppressed serum sensitivity, we hypothesize that serum sensitivity is a consequence of homoserine accumulation. Serum survival is critical for dissemination, an important virulence determinant: thus, together with the essential nature of C. neoformans threonine synthesis, the cross-species serum sensitivity of thr1Delta mutants makes the fungus-specific Thr1p, and likely Thr4p, ideal antifungal drug targets.
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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.