Calcineurin fungi

UNLABELLED: Due to fungal diseases that threaten immunocompromised patients, along with the limited availability of antifungal agents, there is an urgent need for new antifungal compounds to treat fungal infections. Here, we aimed to identify potential antifungal drugs from natural products using the fission yeast Schizosaccharomyces pombe as a model organism since it shares many features with some pathogenic fungi. Here, we identified tubeimoside I (TBMS1), an extract from Chinese herbal medicine, that showed strong antifungal activity against S...

Metarhizium anisopliae is an important class of entomopathogenic fungi used for the biocontrol of insects, but its virulence is affected by insect immunity. We identified a novel FK506 binding protein gene that was differentially expressed between control and Metarhizium-treated Locusta migratoria manilensis. We hypothesized that this protein played an important role in Metarhizium infection of L. migratoria and could provide new insights for developing highly efficient entomopathogenic fungi. We, therefore, cloned the specific gene and obtained its purified protein...

INTRODUCTION: Solid organ transplant (SOT) recipients face an increased susceptibility to invasive fungal infection (IFI) due to filamentous fungi. Post-transplant invasive aspergillosis (IA) and mucormycosis are related to exceedingly high mortality rates and graft loss risk, and its management involve a unique range of clinical challenges. AREAS COVERED: First, the current treatment recommendations for IA and mucormycosis in SOT recipients are critically reviewed, including the supporting evidence...

In nature, the formation of specialized (secondary) metabolites is associated with the late stages of fungal development. Enzymes involved in the biosynthesis of secondary metabolites in fungi are located in distinct subcellular compartments including the cytosol, peroxisomes, endosomes, endoplasmic reticulum, different types of vesicles, the plasma membrane and the cell wall space. The enzymes traffic between these subcellular compartments and the secretion through the plasma membrane are still unclear in the biosynthetic processes of most of these metabolites...

Calcineurin plays critical roles in the virulence of most pathogenic fungi. This study sheds light on those roles in the opportunistic pathogen Candida glabrata using a genome-wide analysis in vitro . The findings could lead to antifungal developments that also avoid immunosuppression.

In pathogenic fungi, calcium-calmodulin-dependent serine-threonine-specific phosphatase calcineurin is involved in morphogenesis and virulence. Therefore, calcineurin and its tightly related protein complexes are attractive antifungal drug targets. However, there is limited knowledge available on the relationship between in vivo Ca2+ -binding sites of calmodulin (CaM) and its functions in regulating stress responses, morphogenesis, and pathogenesis. In the current study, we demonstrated that calmodulin is required for hyphal growth, conidiation, and virulence in the human fungal pathogen, Aspergillus fumigatus ...

Fluconazole is one of the most commonly used antifungals today. A result of this has been the inevitable selection of fluconazole-resistant organisms. This is an especially acute problem in the pathogenic yeast Candida glabrata . Elevated minimal inhibitory concentrations for fluconazole in C. glabrata are frequently associated with substitution mutations within the Zn2Cys6 zinc cluster-containing transcription factor-encoding gene PDR1 . These mutant Pdr1 regulators drive constitutively high expression of target genes like CDR1 that encodes an ATP-binding cassette transporter thought to act as a drug efflux pump...

Calcium (Ca2+ ) is an important second messenger for activating stress response signaling and cell adaptation in eukaryotic cells yet intracellular Ca2+ -dynamics in fungi are poorly understood due to lack of effective real-time Ca2+ reporters. We engineered the GCaMP6f construct for use in the fungal pathogen, Candida albicans , and used live-cell imaging to observe both dynamic Ca2+ spiking and slower changes in non-spiking Ca2+ -GCaMP signals elicited by stress or gene deletion. Short-term exposure to membrane, osmotic or oxidative stress generated immediate stress-specific responses and repeated exposure revealed differential recovery signatures...

Fungal infections are of mounting global concern, and the current limited treatment arsenal poses challenges when treating such infections. In particular, infections by Cryptococcus neoformans are associated with high mortality, emphasizing the need for novel therapeutic options. Calcineurin is a protein phosphatase that mediates fungal stress responses, and calcineurin inhibition by the natural product FK506 blocks C. neoformans growth at 37°C. Calcineurin is also required for pathogenesis. However, because calcineurin is conserved in humans and inhibition with FK506 results in immunosuppression, the use of FK506 as an anti-infective agent is precluded...

Phosphate and calcium ions are nutrients that play key roles in growth, differentiation and the production of bioactive secondary metabolites in filamentous fungi. Phosphate concentration regulates the biosynthesis of hundreds of fungal metabolites. The central mechanisms of phosphate transport and regulation, mediated by the master Pho4 transcriptional factor are known, but many aspects of the control of gene expression need further research. High ATP concentration in the cells leads to inositol pyrophosphate molecules formation, such as IP3 and IP7, that act as phosphorylation status reporters...

BACKGROUND: Aspergillus infection seriously jeopardize the health and safety of life of immunocompromised patients. The emergences of antifungal resistance highlight a demand to find new effective antifungal drugs. Angelica sinensis is a medicine-food herb and phthalides are its characteristic components. A few of phthalides have been reported to display satisfactory antifungal activities against plant pathogenic fungi. However, the structure activity relationships and antifungal action mechanism of phthalides remain to be further explored and elucidated...

Tacrolimus (FK506), an immunosuppressant and calcineurin inhibitor, has fungicidal effects. However, its fungicidal effect is thought to be limited to basidiomycetes, such as Cryptococcus and Malassezia , and not to ascomycetes. FK506 had no fungicidal effect on Candida albicans , C. auris , C. glabrata , C. guilliermondii , C. kefyr , C. krusei , and C. tropicalis (>8 µg/mL); however, C. parapsilosis was susceptible to it at low concentrations of 0.125-0.5 µg/mL. C. metapsilosis and C. orthopsils , previously classified as C...

Maintaining cellular calcium (Ca2+ ) homeostasis is essential for many aspects of cellular life. The high-osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathway responsible for signal integration and transduction plays crucial roles in environmental adaptation, especially in the response to osmotic stress. Hog1 is activated by transient Ca2+ increase in yeast, but the functions of the HOG pathway in Ca2+ homeostasis are largely unknown. We found that the HOG pathway was involved in the regulation of Ca2+ homeostasis in Fusarium graminearum , a devastating fungal pathogen of cereal crops...

To successfully induce disease, Candida albicans must effectively evade the host immune system. One mechanism used by C. albicans to achieve this is to mask immunogenic β(1,3)-glucan epitopes within its cell wall under an outer layer of mannosylated glycoproteins. Consequently, induction of β(1,3)-glucan exposure (unmasking) via genetic or chemical manipulation increases fungal recognition by host immune cells in vitro and attenuates disease during systemic infection in mice. Treatment with the echinocandin caspofungin is one of the most potent drivers of β(1,3)-glucan exposure...

Entomopathogenic fungi are protected by a cell wall with dynamic structure for adapting to various environmental conditions. β-1,3-Glucan recognition proteins activate the innate immune system of insects by recognizing surface molecules of fungi. However, the associations between pathogenicity and the different components of entomopathogenic fungal cell walls remain unclear. Three Beauveria bassiana strains were selected that have significantly differing virulence against Bombyx mori. The molecular mechanisms underlying the immune response in B...

UNLABELLED: Fungal infections are of mounting global concern, and the current limited treatment arsenal poses challenges when treating such infections. In particular, infections by Cryptococcus neoformans are associated with high mortality, emphasizing the need for novel therapeutic options. Calcineurin is a protein phosphatase that mediates fungal stress responses, and calcineurin inhibition by the natural product FK506 blocks C. neoformans growth at 37°C. Calcineurin is also required for pathogenesis...

Calcineurin, a key regulator of the calcium signaling pathway, is involved in calcium signal transduction and calcium ion homeostasis. Magnaporthe oryzae is a devastating filamentous phytopathogenic fungus in rice, yet little is known about the function of the calcium signaling system. Here, we identified a novel calcineurin regulatory-subunit-binding protein, MoCbp7, which is highly conserved in filamentous fungi and was found to localize in the cytoplasm. Phenotypic analysis of the MoCBP7 gene deletion mutant (Δ Mocbp7 ) showed that MoCbp7 influenced the growth, conidiation, appressorium formation, invasive growth, and virulence of M...

BACKGROUND: Trichoderma reesei Rut-C30 is a hypercellulolytic mutant strain that degrades abundant sources of lignocellulosic plant biomass, yielding renewable biofuels. Although Zn2+ is an activator of enzymes in almost all organisms, its effects on cellulase activity in T. reesei have yet to be reported. RESULTS: Although high concentrations of Zn2+ severely suppressed the extension of T. reesei mycelia, the application of 1-4 mM Zn2+ enhanced cellulase and xylanase production in the high-yielding cellulase-producing Rut-C30 strain of T...

This study aimed to investigate the effects of cyclosporine on the morphology, cell wall structure, and secretion characteristics of Cryptococcus neoformans . The minimum inhibitory concentration (MIC) of cyclosporine was found to be 2 µM (2.4 µg/mL) for the H99 strain. Yeast cells treated with cyclosporine at half the MIC showed altered morphology, including irregular shapes and elongated projections, without an effect on cell metabolism. Cyclosporine treatment resulted in an 18-fold increase in chitin and an 8-fold increase in lipid bodies, demonstrating changes in the fungal cell wall structure...

BACKGROUND: Adaptation to alkalinization of the medium in fungi involves an extensive remodeling of gene expression. Komagataella phaffii is an ascomycetous yeast that has become an organism widely used for heterologous protein expression. We explore here the transcriptional impact of moderate alkalinization in this yeast, in search of suitable novel promoters able to drive transcription in response to the pH signal. RESULTS: In spite of a minor effect on growth, shifting the cultures from pH 5...