scholarly journals Amino Acid-Derived 1,2-Benzisothiazolinone Derivatives as Novel Small-Molecule Antifungal Inhibitors: Identification of Potential Genetic Targets

2012 ◽  
Vol 56 (9) ◽  
pp. 4630-4639 ◽  
Author(s):  
Deepu Alex ◽  
Francoise Gay-Andrieu ◽  
Jared May ◽  
Linta Thampi ◽  
Dengfeng Dou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fungal Pathogens ◽  
Structural Similarity ◽  
Homozygous Deletion ◽  
Antifungal Drugs ◽  
Respiratory Pathway ◽  
Phenotypic Data ◽  
Content Type ◽  
Mitochondrial Functions ◽  
Phenotype Analysis

ABSTRACTWe have identified four synthetic compounds (DFD-VI-15, BD-I-186, DFD-V-49, and DFD-V-66) from an amino acid-derived 1,2-benzisothiazolinone (BZT) scaffold that have reasonable MIC50values against a panel of fungal pathogens. These compounds have no structural similarity to existing antifungal drugs. Three of the four compounds have fungicidal activity againstCandidaspp.,Cryptococcus neoformans, and several dermatophytes, while one is fungicidal toAspergillus fumigatus. The kill rates of our compounds are equal to those in clinical usage. The BZT compounds remain active against azole-, polyene-, and micafungin-resistant strains ofCandidaspp. A genetics-based approach, along with phenotype analysis, was used to begin mode of action (MOA) studies of one of these compounds, DFD-VI-15. The genetics-based screen utilized a homozygous deletion collection of approximately 4,700Saccharomyces cerevisiaemutants. We identified mutants that are both hypersensitive and resistant. Using FunSpec, the hypersensitive mutants and a resistantace2mutant clustered within a category of genes related directly or indirectly to mitochondrial functions. InCandida albicans, the functions of the Ace2p transcription factor include the regulation of glycolysis. Our model is that DFD-VI-15 targets a respiratory pathway that limits energy production. Supporting this hypothesis are phenotypic data indicating that DFD-VI-15 causes increased cell-reactive oxidants (ROS) and a decrease in mitochondrial membrane potential. Also, the same compound has activity when cells are grown in a medium containing glycerol (mitochondrial substrate) but is much less active when cells are grown anaerobically.

scholarly journals Whole-Genome Approach to Understanding the Mechanism of Action of a Histatin 5-Derived Peptide

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Cody B. Bullock ◽  
David S. McNabb ◽  
Inés Pinto
Keyword(s):  
Mechanism Of Action ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Content Type ◽  
Histatin 5 ◽  
Amino Acid Peptide ◽  
Killing Activity ◽  
Transport Chain ◽  
Mitochondrial Functions ◽  
Increased Sensitivity

ABSTRACT The incidence of opportunistic fungal infections that threaten immunocompromised patients, along with the limited arsenal of antifungal drugs, calls for renewed efforts to develop novel antifungal therapies. Antimicrobial peptides have garnered interest as potential therapeutics. Among naturally occurring peptides, histatin 5 is a well-characterized 24-amino-acid peptide with strong antifungal activity. Our lab has identified a smaller histatin derivative, KM29, with stronger activity against multiple Candida spp., prompting us to investigate its fungicidal mechanism. A genetic screen was developed to test the Saccharomyces cerevisiae genomewide deletion collection for mutants with increased or decreased peptide sensitivity. The goal was to identify genes that would reveal insights into the mechanism of action of KM29, to be assessed in Candida albicans. Several biological processes yielded increased sensitivity, with endosomal transport and vacuolar function appearing at high frequencies. Among the pathways involved in increased resistance, mitochondrial function showed the highest normalized genome frequency; hence, we focused on characterizing this pathway. KM29 localizes to mitochondria, and the killing activity depends on a functional electron transport chain. In addition, KM29 triggered reactive oxygen species (ROS) production, which was responsible for some cell death but insufficient to account for the complete killing activity. In agreement with this finding, we found that KM29 induced mitochondrial fragmentation and a mild loss of mitochondrial membrane potential. Furthermore, respiratory mutants exhibited severely diminished KM29 uptake. We confirmed this behavior in a C. albicans respiratory mutant. Taking our findings together, this work delineates the mitochondrial functions associated with KM29 fungicidal activity and provides additional pathways for further characterization in Candida spp.

scholarly journals Novel Antifungal Drug Discovery Based on Targeting Pathways Regulating the Fungus-Conserved Upc2 Transcription Factor

2013 ◽  
Vol 58 (1) ◽  
pp. 258-266 ◽  
Author(s):  
Christina Gallo-Ebert ◽  
Melissa Donigan ◽  
Ilana L. Stroke ◽  
Robert N. Swanson ◽  
Melissa T. Manners ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Dna Binding ◽  
Fungal Pathogens ◽  
Direct Interaction ◽  
Antifungal Drugs ◽  
Sterol Biosynthesis ◽  
Content Type ◽  
Stressed Cells

ABSTRACTInfections byCandida albicansand related fungal pathogens pose a serious health problem for immunocompromised patients. Azole drugs, the most common agents used to combat infections, target the sterol biosynthetic pathway. Adaptation to azole therapy develops as drug-stressed cells compensate by upregulating several genes in the pathway, a process mediated in part by the Upc2 transcription factor. We have implemented a cell-based high-throughput screen to identify small-molecule inhibitors of Upc2-dependent induction of sterol gene expression in response to azole drug treatment. The assay is designed to identify not only Upc2 DNA binding inhibitors but also compounds impeding the activation of gene expression by Upc2. An AlphaScreen assay was developed to determine whether the compounds identified interact directly with Upc2 and inhibit DNA binding. Three compounds identified by the cell-based assay inhibited Upc2 protein level andUPC2-LacZgene expression in response to a block in sterol biosynthesis. The compounds were growth inhibitory and attenuated antifungal-induced sterol gene expressionin vivo. They did so by reducing the level of Upc2 protein and Upc2 DNA binding in the presence of drug. The mechanism by which the compounds restrict Upc2 DNA binding is not through a direct interaction, as demonstrated by a lack of DNA binding inhibitory activity using the AlphaScreen assay. Rather, they likely inhibit a novel pathway activating Upc2 in response to a block in sterol biosynthesis. We suggest that the compounds identified represent potential precursors for the synthesis of novel antifungal drugs.

scholarly journals Targeting Methionine Synthase in a Fungal Pathogen Causes a Metabolic Imbalance That Impacts Cell Energetics, Growth, and Virulence

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Jennifer Scott ◽  
Monica Sueiro-Olivares ◽  
Benjamin P. Thornton ◽  
Rebecca A. Owens ◽  
Howbeer Muhamadali ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Aspergillus Fumigatus ◽  
Fungal Pathogen ◽  
Fungal Pathogens ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Methionine Synthase ◽  
Content Type ◽  
Metabolic Imbalance

ABSTRACT There is an urgent need to develop novel antifungals to tackle the threat fungal pathogens pose to human health. Here, we have performed a comprehensive characterization and validation of the promising target methionine synthase (MetH). We show that in Aspergillus fumigatus the absence of this enzymatic activity triggers a metabolic imbalance that causes a reduction in intracellular ATP, which prevents fungal growth even in the presence of methionine. Interestingly, growth can be recovered in the presence of certain metabolites, which shows that metH is a conditionally essential gene and consequently should be targeted in established infections for a more comprehensive validation. Accordingly, we have validated the use of the tetOFF genetic model in fungal research and improved its performance in vivo to achieve initial validation of targets in models of established infection. We show that repression of metH in growing hyphae halts growth in vitro, which translates into a beneficial effect when targeting established infections using this model in vivo. Finally, a structure-based virtual screening of methionine synthases reveals key differences between the human and fungal structures and unravels features in the fungal enzyme that can guide the design of novel specific inhibitors. Therefore, methionine synthase is a valuable target for the development of new antifungals. IMPORTANCE Fungal pathogens are responsible for millions of life-threatening infections on an annual basis worldwide. The current repertoire of antifungal drugs is very limited and, worryingly, resistance has emerged and already become a serious threat to our capacity to treat fungal diseases. The first step to develop new drugs is often to identify molecular targets in the pathogen whose inhibition during infection can prevent its growth. However, the current models are not suitable to validate targets in established infections. Here, we have characterized the promising antifungal target methionine synthase in great detail, using the prominent fungal pathogen Aspergillus fumigatus as a model. We have uncovered the underlying reason for its essentiality and confirmed its druggability. Furthermore, we have optimized the use of a genetic system to show a beneficial effect of targeting methionine synthase in established infections. Therefore, we believe that antifungal drugs to target methionine synthase should be pursued and additionally, we provide a model that permits gaining information about the validity of antifungal targets in established infections.

scholarly journals Pseudohyphal Growth of the Emerging Pathogen Candida auris Is Triggered by Genotoxic Stress through the S Phase Checkpoint

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Gustavo Bravo Ruiz ◽  
Zoe K. Ross ◽  
Neil A. R. Gow ◽  
Alexander Lorenz
Keyword(s):  
Fungal Pathogens ◽  
Genotoxic Stress ◽  
Multidrug Resistant ◽  
S Phase ◽  
Antifungal Drugs ◽  
Yeast Cells ◽  
Candida Auris ◽  
Content Type ◽  
Pseudohyphal Growth ◽  
S Phase Checkpoint

ABSTRACT The morphogenetic switching between yeast cells and filaments (true hyphae and pseudohyphae) is a key cellular feature required for full virulence in many polymorphic fungal pathogens, such as Candida albicans. In the recently emerged yeast pathogen Candida auris, occasional elongation of cells has been reported. However, environmental conditions and genetic triggers for filament formation have remained elusive. Here, we report that induction of DNA damage and perturbation of replication forks by treatment with genotoxins, such as hydroxyurea, methyl methanesulfonate, and the clinically relevant fungistatic 5-fluorocytosine, cause filamentation in C. auris. The filaments formed were characteristic of pseudohyphae and not parallel-sided true hyphae. Pseudohyphal growth is apparently signaled through the S phase checkpoint and, interestingly, is Tup1 independent in C. auris. Intriguingly, the morphogenetic switching capability is strain specific in C. auris, highlighting the heterogenous nature of the species as a whole. IMPORTANCE Candida auris is a newly emerged fungal pathogen of humans. This species was first reported in 2009 when it was identified in an ear infection of a patient in Japan. However, despite intense interest in this organism as an often multidrug-resistant fungus, there is little knowledge about its cellular biology. During infection of human patients, fungi are able to change cell shape from ellipsoidal yeast cells to elongated filaments to adapt to various conditions within the host organism. There are different types of filaments, which are triggered by reactions to different cues. Candida auris fails to form filaments when exposed to triggers that stimulate yeast filament morphogenesis in other fungi. Here, we show that it does form filaments when its DNA is damaged. These conditions might arise when Candida auris cells interact with host immune cells or during growth in certain host tissues (kidney or bladder) or during treatment with antifungal drugs.

scholarly journals Gene Essentiality Analyzed byIn VivoTransposon Mutagenesis and Machine Learning in a Stable Haploid Isolate ofCandida albicans

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Ella Shtifman Segal ◽  
Vladimir Gritsenko ◽  
Anton Levitan ◽  
Bhawna Yadav ◽  
Naama Dror ◽  
...  
Keyword(s):  
Machine Learning ◽  
Candida Albicans ◽  
Fungal Pathogens ◽  
Essential Genes ◽  
Antifungal Drugs ◽  
Model Organisms ◽  
Standard Laboratory ◽  
Genome Database ◽  
Content Type ◽  
Laboratory Conditions

ABSTRACTKnowing the full set of essential genes for a given organism provides important information about ways to promote, and to limit, its growth and survival. For many non-model organisms, the lack of a stable haploid state and low transformation efficiencies impede the use of conventional approaches to generate a genome-wide comprehensive set of mutant strains and the identification of the genes essential for growth. Here we report on the isolation and utilization of a highly stable haploid derivative of the human pathogenic fungusCandida albicans, together with a modified heterologous transposon and machine learning (ML) analysis method, to predict the degree to which all of the open reading frames are required for growth under standard laboratory conditions. We identified 1,610 C. albicansessential genes, including 1,195 with high “essentiality confidence” scores, thereby increasing the number of essential genes (currently 66 in the Candida Genome Database) by >20-fold and providing an unbiased approach to determine the degree of confidence in the determination of essentiality. Among the genes essential inC. albicanswere 602 genes also essential in the model budding and fission yeasts analyzed by both deletion and transposon mutagenesis. We also identified essential genes conserved among the four major human pathogensC. albicans,Aspergillus fumigatus,Cryptococcus neoformans, andHistoplasma capsulatumand highlight those that lack homologs in humans and that thus could serve as potential targets for the design of antifungal therapies.IMPORTANCEComprehensive understanding of an organism requires that we understand the contributions of most, if not all, of its genes. Classical genetic approaches to this issue have involved systematic deletion of each gene in the genome, with comprehensive sets of mutants available only for very-well-studied model organisms. We took a different approach, harnessing the power ofin vivotransposition coupled with deep sequencing to identify >500,000 different mutations, one per cell, in the prevalent human fungal pathogenCandida albicansand to map their positions across the genome. The transposition approach is efficient and less labor-intensive than classic approaches. Here, we describe the production and analysis (aided by machine learning) of a large collection of mutants and the comprehensive identification of 1,610 C. albicansgenes that are essential for growth under standard laboratory conditions. Among theseC. albicansessential genes, we identify those that are also essential in two distantly related model yeasts as well as those that are conserved in all four major human fungal pathogens and that are not conserved in the human genome. This list of genes with functions important for the survival of the pathogen provides a good starting point for the development of new antifungal drugs, which are greatly needed because of the emergence of fungal pathogens with elevated resistance and/or tolerance of the currently limited set of available antifungal drugs.

scholarly journals Precise Expression of Afmed15 Is Crucial for Asexual Development, Virulence, and Survival of Aspergillus fumigatus

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Luyu Guan ◽  
Ruiyang Lu ◽  
Zhengjun Wu ◽  
Guowei Zhong ◽  
Shizhu Zhang
Keyword(s):  
Drug Development ◽  
Aspergillus Fumigatus ◽  
Fungal Pathogens ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Asexual Development ◽  
Fungal Virulence ◽  
Content Type ◽  
Precise Expression

ABSTRACT The rise of drug resistance in fungal pathogens is becoming a serious problem owing to the limited number of antifungal drugs available. Identifying and targeting factors essential for virulence or development unique to fungal pathogens is one approach to develop novel treatments for fungal infections. In this study, we present the identification and functional characterization of a novel developmental regulator in Aspergillus fumigatus, AfMed15, which contained a conserved Med15_fungal domain, as determined by screening of a mutant library that contained more than 2,000 hygromycin-resistant A. fumigatus transformants. Downregulating the expression of Afmed15 abolished the conidiation and decreased the fungal virulence in an insect model. Strikingly, the overexpression of Afmed15 caused fungal death accompanied by intensive autophagy. RNA sequencing of an Afmed15 overexpression strain revealed that altered gene expression patterns were associated with carbon metabolism, energy metabolism, and translation. Interestingly, the addition of metal ions could partially rescue fungal death caused by the overexpression of Afmed15, indicating that disordered ion homeostasis is a potential reason for the fungal death caused by the overexpression of Afmed15. Considering that the precise expression of Afmed15 is crucial for fungal development, virulence, and survival and that no ortholog was found in humans, Afmed15 is an ideal target for antifungal-drug development. IMPORTANCE The identification and characterization of regulators essential for virulence or development constitute one approach for antifungal drug development. In this study, we screened and functionally characterized Afmed15, a novel developmental regulator in A. fumigatus. We demonstrate that the precise transcriptional expression of Afmed15 is crucial for fungal asexual development, virulence, and survival. Downregulating the expression of Afmed15 abolished the conidiation and decreased the fungal virulence in an insect model. In contrast, the overexpression of Afmed15 caused fungal death accompanied by intensive autophagy. Our study provides a foundation for further studies to identify compounds perturbing the expression of Afmed15 that may be used for the prevention of invasive A. fumigatus infections.

scholarly journals Cationic Bioactive Peptide from the Seeds of Benincasa hispida

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Sunayana Sharma ◽  
Hirday Narain Verma ◽  
Nilesh Kumar Sharma
Keyword(s):  
Amino Acid ◽  
Fungal Pathogens ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Potassium Phosphate ◽  
Lipid Peroxide ◽  
Protein Band ◽  
Antifungal Drugs ◽  
Bioactive Peptide ◽  
Benincasa Hispida

A designated bioactive peptide “Hispidalin” purified from the seeds of Benincasa hispida, which is a medicinal plant, belongs to Cucurbitaceae family. Purification was achieved by using a procedure consisting of extraction from potassium phosphate buffer followed by FPLC and HPLC steps. Based on amino acid residue, this peptide is amphipathic and basic with one net positive charge having isoelectric pH 8.1. This peptide is without sulphur containing amino acid suggesting its extended conformation lacking double bond secondary structure. The results obtained from MALDI-TOF suggested that Hispidalin is of molecular mass 5.7 KDa with 49 amino acid residues and confirmed SDS-PAGE resolved ∼6.0 KDa protein band. This novel and unknown peptide “Hispidalin” showed broad and potent inhibitory effects against various human bacterial and fungal pathogens; its growth inhibition was significantly comparable with commercial antibacterial and antifungal drugs. The Hispidalin at 40 μg/mL concentration exhibited 70.8% DPPH free radical-scavenging activity and 69.5% lipid peroxide inhibition. Thus, in the present study, Hispidalin demonstrated remarkable antimicrobial and antioxidant potentials from the seeds of B. hispida.

scholarly journals The Zinc Finger Protein Mig1 Regulates Mitochondrial Function and Azole Drug Susceptibility in the Pathogenic Fungus Cryptococcus neoformans

mSphere ◽  
2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Mélissa Caza ◽  
Guanggan Hu ◽  
Michael Price ◽  
John R. Perfect ◽  
James W. Kronstad
Keyword(s):  
Cryptococcus Neoformans ◽  
Mitochondrial Function ◽  
Drug Susceptibility ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Oxygen Species ◽  
Content Type ◽  
New Targets ◽  
Expression Of Genes ◽  
Mitochondrial Functions

ABSTRACT Fungal pathogens of humans are difficult to treat, and there is a pressing need to identify new targets for antifungal drugs and to obtain a detailed understanding of fungal proliferation in vertebrate hosts. In this study, we examined the roles of the regulatory proteins Mig1 and HapX in mitochondrial function and antifungal drug susceptibility in the fungus Cryptococcus neoformans. This pathogen is a particular threat to the large population of individuals infected with human immunodeficiency virus (HIV). Our analysis revealed regulatory interactions between Mig1 and HapX, and a role for Mig1 in mitochondrial functions, including respiration, tolerance for reactive oxygen species, and expression of genes for iron consumption and iron acquisition functions. Importantly, loss of Mig1 increased susceptibility to the antifungal drug fluconazole, which is commonly used to treat cryptococcal disease. These studies highlight an association between mitochondrial dysfunction and drug susceptibility that may provide new targets for the development of antifungal drugs. The opportunistic pathogen Cryptococcus neoformans causes fungal meningoencephalitis in immunocompromised individuals. In previous studies, we found that the Hap complex in this pathogen represses genes encoding mitochondrial respiratory functions and tricarboxylic acid (TCA) cycle components under low-iron conditions. The orthologous Hap2/3/4/5 complex in Saccharomyces cerevisiae exerts a regulatory influence on mitochondrial functions, and Hap4 is subject to glucose repression via the carbon catabolite repressor Mig1. In this study, we explored the regulatory link between a candidate ortholog of the Mig1 protein and the HapX component of the Hap complex in C. neoformans. This analysis revealed repression of MIG1 by HapX and activation of HAPX by Mig1 under low-iron conditions and Mig1 regulation of mitochondrial functions, including respiration, tolerance for reactive oxygen species, and expression of genes for iron consumption and iron acquisition functions. Consistently with these regulatory functions, a mig1Δ mutant had impaired growth on inhibitors of mitochondrial respiration and inducers of ROS. Furthermore, deletion of MIG1 provoked a dysregulation in nutrient sensing via the TOR pathway and impacted the pathway for cell wall remodeling. Importantly, loss of Mig1 increased susceptibility to fluconazole, thus further establishing a link between azole antifungal drugs and mitochondrial function. Mig1 and HapX were also required together for survival in macrophages, but Mig1 alone had a minimal impact on virulence in mice. Overall, these studies provide novel insights into a HapX/Mig1 regulatory network and reinforce an association between mitochondrial dysfunction and drug susceptibility that may provide new targets for the development of antifungal drugs. IMPORTANCE Fungal pathogens of humans are difficult to treat, and there is a pressing need to identify new targets for antifungal drugs and to obtain a detailed understanding of fungal proliferation in vertebrate hosts. In this study, we examined the roles of the regulatory proteins Mig1 and HapX in mitochondrial function and antifungal drug susceptibility in the fungus Cryptococcus neoformans. This pathogen is a particular threat to the large population of individuals infected with human immunodeficiency virus (HIV). Our analysis revealed regulatory interactions between Mig1 and HapX, and a role for Mig1 in mitochondrial functions, including respiration, tolerance for reactive oxygen species, and expression of genes for iron consumption and iron acquisition functions. Importantly, loss of Mig1 increased susceptibility to the antifungal drug fluconazole, which is commonly used to treat cryptococcal disease. These studies highlight an association between mitochondrial dysfunction and drug susceptibility that may provide new targets for the development of antifungal drugs.

scholarly journals The Candida albicans GAP Gene Family Encodes Permeases Involved in General and Specific Amino Acid Uptake and Sensing

2011 ◽  
Vol 10 (9) ◽  
pp. 1219-1229 ◽  
Author(s):  
Lucie Kraidlova ◽  
Griet Van Zeebroeck ◽  
Patrick Van Dijck ◽  
Hana Sychrová
Keyword(s):  
Amino Acids ◽  
Candida Albicans ◽  
Amino Acid ◽  
Fungal Pathogens ◽  
Signal Transduction Pathway ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Amino Acid Permease ◽  
Content Type ◽  
Six Genes

ABSTRACTTheSaccharomyces cerevisiaegeneral amino acid permease Gap1 (ScGap1) not only mediates the uptake of most amino acids but also functions as a receptor for the activation of protein kinase A (PKA). Fungal pathogens can colonize different niches in the host, each containing various levels of different amino acids and sugars. TheCandida albicansgenome contains six genes homologous to theS. cerevisiae GAP1. The expression of these six genes inS. cerevisiaeshowed that the products of all sixC. albicansgenes differ in their transport capacities.C. albicansGap2 (CaGap2) is the true orthologue ofScGap1 as it transports all tested amino acids. The otherCaGap proteins have narrower substrate specificities thoughCaGap1 andCaGap6 transport several structurally unrelated amino acids.CaGap1,CaGap2, andCaGap6 also function as sensors. Upon detecting some amino acids, e.g., methionine, they are involved in a rapid activation of trehalase, a downstream target of PKA. Our data show thatCaGAPgenes can be functionally expressed inS. cerevisiaeand thatCaGap permeases communicate to the intracellular signal transduction pathway similarly toScGap1.

scholarly journals Adenylyl Cyclase and Protein Kinase A Play Redundant and Distinct Roles in Growth, Differentiation, Antifungal Drug Resistance, and Pathogenicity of Candida auris

mBio ◽  
2021 ◽  
Author(s):  
Ji-Seok Kim ◽  
Kyung-Tae Lee ◽  
Myung Ha Lee ◽  
Eunji Cheong ◽  
Yong-Sun Bahn
Keyword(s):  
Drug Resistance ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Fungal Pathogen ◽  
Fungal Pathogens ◽  
Antifungal Drugs ◽  
Candida Auris ◽  
Content Type ◽  
Antifungal Drug Resistance ◽  
Kinase A

Despite the recently growing concern of pan-resistant Candida auris infection, the pathogenicity of this ascomycetous fungal pathogen and the signaling circuitries governing its resistance to antifungal drugs are largely unknown. Therefore, we analyzed the pathobiological functions of cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway in C. auris , which plays conserved roles in the growth and virulence of fungal pathogens.

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