The Cryptococcus neoformans STRIPAK complex controls genome stability, sexual development, and virulence.

The eukaryotic serine/threonine protein phosphatase PP2A is a heterotrimeric enzyme composed of a scaffold A subunit, a regulatory B subunit, and a catalytic C subunit. Of the four known B subunits, the B"' subunit (known as striatin) interacts with the multi-protein striatin-interacting phosphatase and kinase (STRIPAK) complex. Orthologs of STRIPAK components were identified in Cryptococcus neoformans, namely PP2AA/Tpd3, PP2AC/Pph22, PP2AB/Far8, STRIP/Far11, SLMAP/Far9, and Mob3.

Engineering of Saccharomyces cerevisiae as a platform strain for microbial production of sphingosine-1-phosphate.

Background: Sphingosine-1-phosphate (S1P) is a multifunctional sphingolipid that has been implicated in regulating cellular activities in mammalian cells. Due to its therapeutic potential, there is a growing interest in developing efficient methods for S1P production. To date, the production of S1P has been achieved through chemical synthesis or blood extraction, but these processes have limitations such as complexity and cost.

Discovery and Optimization of a Series of Vinyl Sulfoximine-Based Analogues as Potent Nrf2 Activators for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the central nervous system (CNS), which leads to demyelination, axonal loss, and neurodegeneration. Increased oxidative stress and neurodegeneration have been implicated in all stages of MS, making neuroprotective therapeutics a promising strategy for its treatment. We previously have reported vinyl sulfones with antioxidative and anti-inflammatory properties that activate nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that induces the expression of cytoprotective genes against oxidative stress.

The STRIPAK complex controls genome stability, sexual development, and virulence.

The eukaryotic serine/threonine protein phosphatase PP2A is a heterotrimeric enzyme composed of a scaffold A subunit, a regulatory B subunit, and a catalytic C subunit. Of the four known B subunits, the B"' subunit (known as striatin) interacts with the multi-protein striatin-interacting phosphatase and kinase (STRIPAK) complex. Orthologs of STRIPAK components were identified in , namely PP2AA/Tpd3, PP2AC/Pph22, PP2AB/Far8, STRIP/Far11, SLMAP/Far9, and Mob3.

Sensing and responding to host-derived stress signals: lessons from fungal meningitis pathogen.

The sophisticated ability of living organisms to sense and respond to external stimuli is critical for survival. This is particularly true for fungal pathogens, where the capacity to adapt and proliferate within a host is essential. To this end, signaling pathways, whether evolutionarily conserved or unique, have been refined through interactions with the host.

Comprehensive Overview of : An Emerging Multidrug-Resistant Fungal Pathogen.

The rise of , a multidrug-resistant fungal pathogen, across more than 40 countries, has signaled an alarming threat to global health due to its significant resistance to existing antifungal therapies. Characterized by its rapid spread and robust drug resistance, presents a critical challenge in managing infections, particularly in healthcare settings. With research on its biological traits and genetic basis of virulence and resistance still in the early stages, there is a pressing need for a concerted effort to understand and counteract this pathogen.

Unraveling the cryptic functions of mitogen-activated protein kinases Cpk2 and Mpk2 in .

Mitogen-activated protein kinase (MAPK) pathways are fundamental to the regulation of biological processes in eukaryotic organisms. The basidiomycete , known for causing fungal meningitis worldwide, possesses five MAPKs. Among these, Cpk1, Hog1, and Mpk1 have established roles in sexual reproduction, stress responses, and cell wall integrity.

Evaluation of exposure to cyanogenic glycosides and potential hydrogen cyanide release in commercially available foods among the Korean population.

The release of hydrogen cyanide (HCN) after food ingestion can pose a serious health risk to consumers. This study aimed to simultaneously quantify four cyanogenic glycosides (lotaustralin, prunasin, taxiphyllin, and dhurrin) using liquid chromatography-tandem mass spectrometry. The analysis scope extended beyond agricultural products to various consumer foods to estimate dietary exposure to cyanogenic glycosides and assess its risk levels.

Pleiotropic roles of LAMMER kinase, Lkh1 in stress responses and virulence of .

Dual-specificity LAMMER kinases are highly evolutionarily conserved in eukaryotes and play pivotal roles in diverse physiological processes, such as growth, differentiation, and stress responses. Although the functions of LAMMER kinase in fungal pathogens in pathogenicity and stress responses have been characterized, its role in , a human fungal pathogen and a model yeast of basidiomycetes, remains elusive. In this study, we identified a homologous gene and constructed a strain with a deleted and a complemented strain.

Casein kinase 2 complex: a central regulator of multiple pathobiological signaling pathways in .

The casein kinase 2 (CK2) complex has garnered extensive attention over the past decades as a potential therapeutic target for diverse human diseases, including cancer, diabetes, and obesity, due to its pivotal roles in eukaryotic growth, differentiation, and metabolic homeostasis. While CK2 is also considered a promising antifungal target, its role in fungal pathogens remains unexplored. In this study, we investigated the functions and regulatory mechanisms of the CK2 complex in , a major cause of fungal meningitis.

Sua5 catalyzing universal tA tRNA modification is responsible for multifaceted functions of the KEOPS complex in .

The N-threonylcarbamoyl adenosine (tA) tRNA modification is critical for ensuring translation fidelity across three domains of life. Our prior work highlighted the KEOPS complex, organized in a Pcc1-Kae1-Bud32-Cgi121 linear arrangement, not only serves an evolutionarily conserved role in tA tRNA modification but also exerts diverse functional impacts on pathobiological characteristics in , a leading cause of fungal meningitis worldwide. However, the extent to which the pleiotropic functions of the KEOPS complex are specifically tied to tRNA modification remains uncertain.

Functional Characterization of DNA N-Glycosylase Ogg1 and Ntg1 in DNA Damage Stress of Cryptococcus neoformans.

Reactive oxygen species induce DNA strand breaks and DNA oxidation. DNA oxidation leads to DNA mismatches, resulting in mutations in the genome if not properly repaired. Homologous recombination (HR) and non-homologous end-joining (NHEJ) are required for DNA strand breaks, whereas the base excision repair system mainly repairs oxidized DNAs, such as 8-oxoguanine and thymine glycol, by cleaving the glycosidic bond, inserting correct nucleotides, and sealing the gap.

Integrated genomics and phenotype microarray analysis of Saccharomyces cerevisiae industrial strains for rice wine fermentation and recombinant protein production.

The industrial potential of Saccharomyces cerevisiae has extended beyond its traditional use in fermentation to various applications, including recombinant protein production. Herein, comparative genomics was performed with three industrial S. cerevisiae strains and revealed a heterozygous diploid genome for the 98-5 and KSD-YC strains (exploited for rice wine fermentation) and a haploid genome for strain Y2805 (used for recombinant protein production).

The hybrid RAVE complex plays V-ATPase-dependent and -independent pathobiological roles in Cryptococcus neoformans.

V-ATPase, which comprises 13-14 subunits, is essential for pH homeostasis in all eukaryotes, but its proper function requires a regulator to assemble its subunits. While RAVE (regulator of H+-ATPase of vacuolar and endosomal membranes) and Raboconnectin-3 complexes assemble V-ATPase subunits in Saccharomyces cerevisiae and humans, respectively, the function of the RAVE complex in fungal pathogens remains largely unknown. In this study, we identified two RAVE complex components, Rav1 and Wdr1, in the fungal meningitis pathogen Cryptococcus neoformans, and analyzed their roles.

Secreted aspartyl protease 3 regulated by the Ras/cAMP/PKA pathway promotes the virulence of .

The surge of multidrug-resistant fungal pathogens, especially , poses significant threats to global public health. exhibits resistance to multiple antifungal drugs, leading to major outbreaks and a high mortality rate. With an urgent call for innovative therapeutic strategies, this study focused on the regulation and pathobiological significance of secreted aspartyl proteinases (SAPs) in , as these enzymes play pivotal roles in the virulence of some fungal species.

Protein Kinase A Controls the Melanization of through the Alteration of Cell Wall Components.

, a multidrug-resistant fungal pathogen, significantly threatens global public health. Recent studies have identified melanin production, a key virulence factor in many pathogenic fungi that protects against external threats like reactive oxygen species, in . However, the melanin regulation mechanism remains elusive.

Deciphering the regulatory mechanisms of the cAMP/protein kinase A pathway and their roles in the pathogenicity of .

The emergence of multidrug-resistant fungal pathogens is a significant concern for global public health. poses a considerable threat as a multidrug-resistant fungal pathogen. Our recent study revealed that the adenylyl cyclase Cyr1 and protein kinase A (PKA) pathways play distinct and redundant roles in drug resistance and pathogenicity of .

Adenylyl-Sulfate Kinase (Met14)-Dependent Cysteine and Methionine Biosynthesis Pathways Contribute Distinctively to Pathobiological Processes in Cryptococcus neoformans.

Blocking of nutrient uptake and amino acid biosynthesis are considered potential targets for next-generation antifungal drugs against pathogenic fungi, including Cryptococcus neoformans. In this regard, the sulfate assimilation pathway is particularly attractive, as it is only present in eukaryotes such as plants and fungi, yet not in mammals. Here, we demonstrated that the adenylyl sulfate kinase (Met14) in the sulfate assimilation pathway is not essential yet is required for the viability of C.

Dysregulating PHO Signaling via the CDK Machinery Differentially Impacts Energy Metabolism, Calcineurin Signaling, and Virulence in Cryptococcus neoformans.

Fungal pathogens uniquely regulate phosphate homeostasis via the cyclin-dependent kinase (CDK) signaling machinery of the phosphate acquisition (PHO) pathway (Pho85 kinase-Pho80 cyclin-CDK inhibitor Pho81), providing drug-targeting opportunities. Here, we investigate the impact of a PHO pathway activation-defective Cryptococcus neoformans mutant (Δ) and a constitutively activated PHO pathway mutant (Δ) on fungal virulence. Irrespective of phosphate availability, the PHO pathway was derepressed in Δ with all phosphate acquisition pathways upregulated and much of the excess phosphate stored as polyphosphate (polyP).

Evaluation and Monitoring of the Natural Toxin Ptaquiloside in Bracken Fern, Meat, and Dairy Products.

Ptaquiloside, a naturally occurring cancer-causing substance in bracken fern, has been detected in the meat and milk of cows fed a diet containing bracken fern. A rapid and sensitive method for the quantitative analysis of ptaquiloside in bracken fern, meat, and dairy products was developed using the QuEChERS method and liquid chromatography-tandem mass spectrometry. The method was validated according to the Association of Official Analytical Chemists guidelines and met the criteria.

Extension of -Linked Mannosylation in the Golgi Apparatus Is Critical for Cell Wall Integrity Signaling and Interaction with Host Cells in Cryptococcus neoformans Pathogenesis.

The human-pathogenic yeast Cryptococcus neoformans assembles two types of -linked glycans on its proteins. In this study, we identified and functionally characterized the C. neoformans gene, encoding an α1,3-mannosyltransferase responsible for the second mannose addition to minor -glycans containing xylose in the Golgi apparatus.

Unraveling Capsule Biosynthesis and Signaling Networks in Cryptococcus neoformans.

The polysaccharide capsule of Cryptococcus neoformans-an opportunistic basidiomycete pathogen and the major etiological agent of fungal meningoencephalitis-is a key virulence factor that prevents its phagocytosis by host innate immune cells. However, the complex signaling networks for their synthesis and attachment remain elusive. In this study, we systematically analyzed capsule biosynthesis and signaling networks using C.

Essential Roles of Ribonucleotide Reductases under DNA Damage and Replication Stresses in Cryptococcus neoformans.

A balance in the deoxyribonucleotide (dNTPs) intracellular concentration is critical for the DNA replication and repair processes. In the model yeast Saccharomyces cerevisiae, the Mec1-Rad53-Dun1 kinase cascade mainly regulates the ribonucleotide reductase (RNR) gene expression during DNA replication and DNA damage stress. However, the RNR regulatory mechanisms in basidiomycete fungi during DNA replication and damage stress remain elusive.