Adaptation to Endoplasmic Reticulum Stress in Relies on the Activity of the Hog1 Mitogen-Activated Protein Kinase.

Adaptation to ER stress is linked to the pathogenicity of . The fungus responds to ER stress primarily by activating the conserved Ire1-Hac1-dependent unfolded protein response (UPR) pathway. Subsequently, when ER homeostasis is re-established, the UPR is attenuated in a timely manner, a facet that is unexplored in .

Functional characterization of a high-affinity iron transporter (PiFTR) from the endophytic fungus Piriformospora indica and its role in plant growth and development.

Iron (Fe) is a micronutrient required for plant growth and development; however, most Fe forms in soil are not readily available to plants, resulting in low Fe contents in plants and, thereby, causing Fe deficiency in humans. Biofortification through plant-fungal co-cultivation might be a sustainable approach to increase crop Fe contents. Therefore, we aimed to examine the role of a Piriformospora indica Fe transporter on rice Fe uptake under low Fe conditions.

The protein kinase Ire1 impacts pathogenicity of Candida albicans by regulating homeostatic adaptation to endoplasmic reticulum stress.

The unfolded protein response (UPR), crucial for the maintenance of endoplasmic reticulum (ER) homeostasis, is tied to the regulation of multiple cellular processes in pathogenic fungi. Here, we show that Candida albicans relies on an ER-resident protein, inositol-requiring enzyme 1 (Ire1) for sensing ER stress and activating the UPR. Compromised Ire1 function impacts cellular processes that are dependent on functional secretory homeostasis, as inferred from transcriptional profiling.

Ifu5, a WW domain-containing protein interacts with Efg1 to achieve coordination of normoxic and hypoxic functions to influence pathogenicity traits in Candida albicans.

Hypoxic adaptation pathways, essential for Candida albicans pathogenesis, are tied to its transition from a commensal to a pathogen. Herein, we identify a WW domain-containing protein, Ifu5, as a determinant of hypoxic adaptation that also impacts normoxic responses in this fungus. Ifu5 activity supports glycosylation homeostasis via the Cek1 mitogen-activated protein kinase-dependent up-regulation of PMT1, under normoxia.

Molecular studies of NAD- and NADP-glutamate dehydrogenases decipher the conundrum of yeast-hypha dimorphism in zygomycete Benjaminiella poitrasii.

Benjaminiella poitrasii, a zygomycete, shows glucose- and temperature-dependent yeast (Y)-hypha (H) dimorphic transition. Earlier, we reported the biochemical correlation of relative proportion of NAD- and NADP-glutamate dehydrogenases (GDHs) with Y-H transition. Further, we observed the presence of one NAD-GDH and two form-specific NADP-GDH isoenzymes in B.

Controlling pathogenesis in Candida albicans by targeting Efg1 and Glyoxylate pathway through naturally occurring polyphenols.

Candida albicans has frequently shown resistance to azoles, the commonly used antifungal drugs. Efg1 has dual role under normoxia and hypoxia supporting infection. It is the major regulator of morphogenesis in C.

Sef1-Regulated Iron Regulon Responds to Mitochondria-Dependent Iron-Sulfur Cluster Biosynthesis in .

Iron homeostasis mechanisms allow the prime commensal-pathogen to cope with the profound shift in iron levels in the mammalian host. The regulators, Sef1 and Sfu1 influence activation and repression of genes required for iron uptake and acquisition by inducing the expression of iron regulon genes in iron-deplete conditions and inactivating them in iron-replete condition. Our study for the first time shows that coordinates the activation of the iron regulon with the mitochondrial use of iron for Fe-S cluster biosynthesis, a cellular process that is connected to cellular iron metabolism.

The Significance of Lipids to Biofilm Formation in : An Emerging Perspective.

, the dimorphic opportunistic human fungal pathogen, is capable of forming highly drug-resistant biofilms in the human host. Formation of biofilm is a multistep and multiregulatory process involving various adaptive mechanisms. The ability of cells in a biofilm to alter membrane lipid composition is one such adaptation crucial for biofilm development in .

The activity of RTA2, a downstream effector of the calcineurin pathway, is required during tunicamycin-induced ER stress response in Candida albicans.

In this study, we demonstrate a novel function of a downstream effector molecule of the calcineurin pathway, RTA2 (Resistance To Aminocholesterol), in ER stress response. The deletion of RTA2 increases susceptibility to the ER stressor tunicamycin and morpholine-like drug, 7-aminocholesterol. Additionally, the expression of RTA2 is also transcriptionally induced by ergosterol biosynthesis inhibitors and cell-wall-damaging agents.

Mitochondria influence CDR1 efflux pump activity, Hog1-mediated oxidative stress pathway, iron homeostasis, and ergosterol levels in Candida albicans.

Mitochondrial dysfunction in Candida albicans is known to be associated with drug susceptibility, cell wall integrity, phospholipid homeostasis, and virulence. In this study, we deleted CaFZO1, a key component required during biogenesis of functional mitochondria. Cells with FZO1 deleted displayed fragmented mitochondria, mitochondrial genome loss, and reduced mitochondrial membrane potential and were rendered sensitive to azoles and peroxide.

Membrane homoeostasis and multidrug resistance in yeast.

The development of MDR (multidrug resistance) in yeast is due to a number of mechanisms. The most documented mechanism is enhanced extrusion of drugs mediated by efflux pump proteins belonging to either the ABC (ATP-binding cassette) superfamily or MFS (major facilitator superfamily). These drug-efflux pump proteins are localized on the plasma membrane, and the milieu therein affects their proper functioning.

Transcriptional activation and increased mRNA stability contribute to overexpression of CDR1 in azole-resistant Candida albicans.

Many azole-resistant (AR) clinical isolates of Candida albicans display increased expression of the drug transporters CDR1 and CDR2. In this study, we evaluate the molecular mechanisms that contribute to the maintenance of constitutively high CDR1 transcript levels in two matched pairs of azole-susceptible (AS) and AR clinical isolates of C. albicans.

Multidrug transporters CaCdr1p and CaMdr1p of Candida albicans display different lipid specificities: both ergosterol and sphingolipids are essential for targeting of CaCdr1p to membrane rafts.

In this study, we compared the effects of altered membrane lipid composition on the localization of two membrane drug transporters from different superfamilies of the pathogenic yeast Candida albicans. We demonstrated that in comparison to the major facilitator superfamily multidrug transporter CaMdr1p, ATP-binding cassette transporter CaCdr1p of C. albicans is preferentially localized within detergent-resistant membrane (DRM) microdomains called 'rafts.

Long chain base tolerance in Saccharomyces cerevisiae is induced by retrograde signals from the mitochondria.

Saccharomyces cerevisiae cells lacking their mitochondrial DNA (rho0 cells) respond to this loss of genetic information by induction of a program of nuclear gene expression called the retrograde response. Expression of genes involved in multidrug resistance and sphingolipid biosynthesis is coordinately induced in rho0 cells by the zinc cluster transcription factor Pdr3p. In this report, we identify a membrane protein involved in control of intracellular levels of a sphingolipid precursor as a transcriptional target of the Pdr3p-mediated retrograde response.

Transcriptional regulation by Lge1p requires a function independent of its role in histone H2B ubiquitination.

Saccharomyces cerevisiae cells that have lost their mitochondrial genome (rho(0)) strongly induce transcription of multidrug resistance genes, including the ATP-binding cassette transporter gene PDR5. PDR5 induction in rho(0) cells requires the presence of the zinc cluster transcription factor Pdr3p. The PDR3 gene is positively autoregulated in rho(0) cells by virtue of the presence of two binding sites for Pdr3p in its promoter.

MFalpha1, the gene encoding the alpha mating pheromone of Candida albicans.

Candida albicans, the single most frequently isolated human fungal pathogen, was thought to be asexual until the recent discovery of the mating-type-like locus (MTL). Homozygous MTL strains were constructed and shown to mate. Furthermore, it has been demonstrated that opaque-phase cells are more efficient in mating than white-phase cells.

Drug resistance in yeasts--an emerging scenario.

In view of the increasing threat posed by fungal infections in immunocompromised patients and due to the non-availability of effective treatments, it has become imperative to find novel antifungals and vigorously search for new drug targets. Fungal pathogens acquire resistance to drugs (antifungals), a well-established phenomenon termed multidrug resistance (MDR), which hampers effective treatment strategies. The MDR phenomenon is spread throughout the evolutionary scale.