Cryptococcus neoformans is the leading cause of fungal meningitis in immunocomprised populations. Although extensive studies have been conducted on signal transduction pathways important for fungal sexual reproduction and virulence, how fungal virulence is regulated during infection is still not understood. In this study, we identified the F-box protein Fbp1, which contains a putative F-box domain and 12 leucine-rich repeats (LRR). Although fbp1 mutants showed normal growth and produced normal major virulence factors, such as melanin and capsule, Fbp1 was found to be essential for fungal virulence, as fbp1 mutants were avirulent in a murine systemic-infection model. Fbp1 is also important for fungal sexual reproduction. Basidiospore production was blocked in bilateral mating between fbp1 mutants, even though normal dikaryotic hyphae were observed during mating. In vitro assays of stress responses revealed that fbp1 mutants are hypersensitive to SDS, but not calcofluor white (CFW) or Congo red, indicating that Fbp1 may regulate cell membrane integrity. Fbp1 physically interacts with Skp1 homologues in both Saccharomyces cerevisiae and C. neoformans via its F-box domain, suggesting it may function as part of an SCF (Skp1, Cullins, F-box proteins) E3 ligase. Overall, our study revealed that the F-box protein Fbp1 is essential for fungal sporulation and virulence in C. neoformans, which likely represents a conserved novel virulence control mechanism that involves the SCF E3 ubiquitin ligase-mediated proteolysis pathway.
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http://dx.doi.org/10.1128/EC.00004-11 | DOI Listing |
Genes (Basel)
August 2024
Department of Biological Sciences, University of New Orleans, New Orleans, LA 70148, USA.
Multiple transcription factors in the budding yeast are required for the switch from fermentative growth to respiratory growth. The Hap2/3/4/5 complex is a transcriptional activator that binds to CCAAT sequence elements in the promoters of many genes involved in the tricarboxylic acid cycle and oxidative phosphorylation and activates gene expression. Adr1 and Cat8 are required to activate the expression of genes involved in the glyoxylate cycle, gluconeogenesis, and utilization of nonfermentable carbon sources.
View Article and Find Full Text PDFmBio
October 2024
Graduate School of Biomedical Sciences, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
Fungal pathogens are underappreciated causes of significant morbidity and mortality worldwide. In previous studies, we determined that a heat-killed, fbp1-deficient strain (HK-fbp1) is a potent vaccine candidate. We determined that vaccination with HK-fbp1 confers protective immunity against lethal Cryptococcosis in an interferon γ (IFNγ)-dependent manner.
View Article and Find Full Text PDFSheng Wu Gong Cheng Xue Bao
May 2024
Key Laboratory of Functional Yeast of China Light Industry, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, Hubei, China.
Commun Biol
July 2023
Department of Molecular Diagnosis, Graduate School of Medicine Chiba University, Chiba, 260-8670, Japan.
Fructose-1,6-bisphosphatase (FBPase) deficiency, caused by an FBP1 mutation, is an autosomal recessive disorder characterized by hypoglycemic lactic acidosis. Due to the rarity of FBPase deficiency, the mechanism by which the mutations cause enzyme activity loss still remains unclear. Here we identify compound heterozygous missense mutations of FBP1, c.
View Article and Find Full Text PDFArch Biochem Biophys
July 2023
Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, 110004, China. Electronic address:
Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive disorder characterized by impaired gluconeogenesis caused by mutations in the fructose-1,6-bisphosphatase 1 (FBP1) gene. The molecular mechanisms underlying FBPase deficiency caused by FBP1 mutations require investigation. Herein, we report the case of a Chinese boy with FBPase deficiency who presented with hypoglycemia, ketonuria, metabolic acidosis, and repeated episodes of generalized seizures that progressed to epileptic encephalopathy.
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