Lethal metabolism of Candida albicans respiratory mutants.

The destructive impact of fungi in agriculture and animal and human health, coincident with increases in antifungal resistance, underscores the need for new and alternative drug targets to counteract these trends. Cellular metabolism relies on many intermediates with intrinsic toxicity and promiscuous enzymatic activity generates others. Fuller knowledge of these toxic entities and their generation may offer opportunities of antifungal development.

Unique, Diverged, and Conserved Mitochondrial Functions Influencing Candida albicans Respiration.

is an opportunistic fungal pathogen of major clinical concern. The virulence of this pathogen is intimately intertwined with its metabolism. Mitochondria, which have a central metabolic role, have undergone many lineage-specific adaptations in association with their eukaryotic host.

The PHR Family: The Role of Extracellular Transglycosylases in Shaping Candida albicans Cells.

is an opportunistic microorganism that can become a pathogen causing mild superficial mycosis or more severe invasive infections that can be life-threatening for debilitated patients. In the etiology of invasive infections, key factors are the adaptability of to the different niches of the human body and the transition from a yeast form to hypha. Hyphal morphology confers high adhesiveness to the host cells, as well as the ability to penetrate into organs.

Grf10 and Bas1 Regulate Transcription of Adenylate and One-Carbon Biosynthesis Genes and Affect Virulence in the Human Fungal Pathogen .

is an opportunistic human fungal pathogen that causes superficial fungal infections and lethal systemic infections. To colonize and establish infections, coordinates the expression of virulence and metabolic genes. Previous work showed that the homeodomain transcription factor Grf10 is required for formation of hyphae, a virulence factor.

Dynamic time warping assessment of high-resolution melt curves provides a robust metric for fungal identification.

Fungal infections are a global problem imposing considerable disease burden. One of the unmet needs in addressing these infections is rapid, sensitive diagnostics. A promising molecular diagnostic approach is high-resolution melt analysis (HRM).

Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling.

Background: The cell wall is essential for the yeast to hypha (Y-H) transition that enables Candida albicans to invade human tissues and evade the immune system. The main constituent, β(1,3)-glucan, is remodeled by glucanosyltransferases of the GH72 family. Phr1p is responsible of glucan remodeling at neutral-alkaline pH and is essential for morphogenesis and virulence.

The GRF10 homeobox gene regulates filamentous growth in the human fungal pathogen Candida albicans.

Candida albicans is the most common human fungal pathogen and can cause life-threatening infections. Filamentous growth is critical in the pathogenicity of C. albicans, as the transition from yeast to hyphal forms is linked to virulence and is also a pivotal process in fungal biofilm development.

Phr1p, a glycosylphosphatidylinsitol-anchored β(1,3)-glucanosyltransferase critical for hyphal wall formation, localizes to the apical growth sites and septa in Candida albicans.

Cell wall biogenesis is a dynamic process relying on the coordinated activity of several extracellular enzymes. PHR1 is a pH-regulated gene of Candida albicans encoding a glycosylphosphatidylinositol-anchored β(1,3)-glucanosyltransferase of family GH72 which acts as a cell wall remodelling enzyme and is crucial for morphogenesis and virulence. In order to explore the function of Phr1p, we obtained a green fluorescent protein (GFP) fusion to determine its localization.

Enzymatic dysfunction of mitochondrial complex I of the Candida albicans goa1 mutant is associated with increased reactive oxidants and cell death.

We have previously shown that deletion of GOA1 (growth and oxidant adaptation) of Candida albicans results in a loss of mitochondrial membrane potential, ATP synthesis, increased sensitivity to oxidants and killing by human neutrophils, and avirulence in a systemic model of candidiasis. We established that translocation of Goa1p to mitochondria occurred during peroxide stress. In this report, we show that the goa1Δ (GOA31), compared to the wild type (WT) and a gene-reconstituted (GOA32) strain, exhibits sensitivity to inhibitors of the classical respiratory chain (CRC), including especially rotenone (complex I [CI]) and salicylhydroxamic acid (SHAM), an inhibitor of the alternative oxidase pathway (AOX), while potassium cyanide (KCN; CIV) causes a partial inhibition of respiration.

Regulation of innate immune response to Candida albicans infections by αMβ2-Pra1p interaction.

Candida albicans is a common opportunistic fungal pathogen and is the leading cause of invasive fungal diseases in immunocompromised individuals. The induction of cell-mediated immunity to C. albicans is one of the main tasks of cells of the innate immune system, and in vitro evidence suggests that integrin α(M)β₂ (CR3, Mac-1, and CD11b/CD18) is the principal leukocyte receptor involved in recognition of the fungus.

PHR1, a pH-regulated gene of Candida albicans encoding a glucan-remodelling enzyme, is required for adhesion and invasion.

The fungal cell wall plays a crucial role in host-pathogen interactions. Its formation is the result of the coordinated activity of several extracellular enzymes, which assemble the constituents, and remodel and hydrolyse them in the extracellular space. Candida albicans Phr1 and Phr2 proteins belong to family GH72 of the beta-(1,3)-glucanosyltransferases and play a crucial role in cell wall assembly.

Goa1p of Candida albicans localizes to the mitochondria during stress and is required for mitochondrial function and virulence.

Using a Tn7 transposon library of Candida albicans, we have identified a mutant that exhibited sensitivity in drop plate assays to oxidants such as menadione and hydrogen peroxide. To verify the role of the mutated gene in stress adaptation, null mutants were constructed and phenotypically characterized. Because of its apparent functions in growth and oxidant adaptation, we have named the gene GOA1.

The protein secretory pathway of Candida albicans.

Virulence of the opportunistic pathogen, Candida albicans, relies on an assemblage of attributes. These include the secretion of hydrolytic enzymes, cell surface adhesins, morphological transition between yeast and hyphae, phenotypic switching and biofilm formation. These diverse features are united by their dependence on the protein secretory apparatus for expression.

Genetic transformation of Candida albicans.

Genetic transformation is the primary method of genetic manipulation of Candida albicans. The lack of a complete sexual cycle prevents application of classical genetic analyses. However, transformation permits introduction into the genome of a wide variety of defined mutations including deletions, insertions, and fusions.

GLN3 encodes a global regulator of nitrogen metabolism and virulence of C. albicans.

The function of GLN3, a GATA factor encoding gene, in nitrogen metabolism of Candida albicans was examined. GLN3 null mutants had reduced growth rates on multiple nitrogen sources. More severe growth defects were observed in mutants lacking both GLN3 and GAT1, a second GATA factor gene.

Identification of pH-regulated antigen 1 released from Candida albicans as the major ligand for leukocyte integrin alphaMbeta2.

Candida albicans is a common opportunistic fungal pathogen and is the leading cause of invasive fungal disease in immunocompromised individuals. The induction of cell-mediated immunity to C. albicans is of critical importance in host defense and the prime task of cells of the innate immune system.

Flanking direct repeats of hisG alter URA3 marker expression at the HWP1 locus of Candida albicans.

HWP1 encodes an adhesin of Candida albicans and has been implicated in filamentation and virulence. URA3, an often-used transformation selection marker, is apparently incorrectly expressed when integrated at the HWP1 locus, which results in an attenuated virulence phenotype. Expression of URA3 is compromised by ectopic integration at other loci as well.

Analysis of heterologous expression of Candida albicans SEC61 gene reveals differences in Sec61p homologues related to species-specific functionality.

The protein secretory pathway has not been studied in depth in Candida albicans despite its essential role in the secretion of enzymes and cell surface components related to the ability of the fungus to colonize the human host. To gain further insight into the elements that participate in the first stages of the secretory process in this fungal pathogen we have isolated and characterized the C. albicans ortholog of SEC61.

Nitrogen metabolism and virulence of Candida albicans require the GATA-type transcriptional activator encoded by GAT1.

Nitrogen acquisition and metabolism is central to microbial growth. A conserved family of zinc-finger containing transcriptional regulators known as GATA-factors ensures efficient utilization of available nitrogen sources by fungi. GATA factors activate expression of nitrogen catabolic pathways when preferred nitrogen sources are absent or limiting, a phenomenon known as nitrogen catabolite repression.

Diverged binding specificity of Rim101p, the Candida albicans ortholog of PacC.

The biology of Candida albicans, including dimorphism and virulence, is significantly influenced by environmental pH. The response to ambient pH includes the pH-conditional expression of several genes, which is directly or indirectly regulated by Rim101p. Rim101p is homologous to PacC, a transcription factor that regulates pH-conditional gene expression in Aspergillus nidulans.

Conserved serine/threonine kinase encoded by CBK1 regulates expression of several hypha-associated transcripts and genes encoding cell wall proteins in Candida albicans.

The opportunistic fungal pathogen, Candida albicans, is reported to have several potential virulence factors. A potentially significant factor is the ability to undergo morphological transition from yeast to hypha. This alteration of form is accompanied by many changes within the cell, including alterations in gene expression and cell wall composition.

Allele-specific gene targeting in Candida albicans results from heterology between alleles.

The opportunistic fungal pathogen Candida albicans is asexual and diploid. Thus, introduction of recessive mutations requires targeted gene replacement of two alleles to effect expression of a recessive phenotype. This is often performed by recycling of a URA3 marker gene that is flanked by direct repeats of hisG.