scholarly journals N-Acetylglucosamine (GlcNAc) Sensing, Utilization, and Functions in Candida albicans

2020 ◽  
Vol 6 (3) ◽  
pp. 129 ◽  
Author(s):  
Han Du ◽  
Craig L. Ennis ◽  
Aaron D. Hernday ◽  
Clarissa J. Nobile ◽  
Guanghua Huang
Keyword(s):  
Candida Albicans ◽  
Fungal Species ◽  
Phenotypic Switch ◽  
Fungal Cell ◽  
The Past ◽  
Amide Derivative ◽  
Major Nutrient ◽  
Morphological Transitions ◽  
Opportunistic Fungal Pathogen ◽  
Eukaryotic Organisms

The sensing and efficient utilization of environmental nutrients are critical for the survival of microorganisms in environments where nutrients are limited, such as within mammalian hosts. Candida albicans is a common member of the human microbiota as well as an opportunistic fungal pathogen. The amide derivative sugar N-acetlyglucosamine (GlcNAc) is an important signaling molecule for C. albicans that could be a major nutrient source for this fungus in host settings. In this article, we review progress made over the past two decades on GlcNAc utilization, sensing, and functions in C. albicans and its related fungal species. GlcNAc sensing and catabolic pathways have been intensively studied in C. albicans. The C. albicans protein Ngt1 represents the first identified GlcNAc-specific transporter in eukaryotic organisms. In C. albicans, GlcNAc not only induces morphological transitions including the yeast to hyphal transition and the white to opaque phenotypic switch, but it also promotes fungal cell death. The Ras-cAMP/PKA signaling pathway plays critical roles in regulating these processes. Given the importance of GlcNAc sensing and utilization in C. albicans, targeting GlcNAc associated pathways and key pathway components could be promising in the development of new antifungal strategies.

scholarly journals In Fungal Intracellular Pathogenesis, Form Determines Fate

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Robin C. May ◽  
Arturo Casadevall
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Membrane Integrity ◽  
Pathogenic Fungi ◽  
Morphological Transition ◽  
Physical Damage ◽  
Fungal Cell ◽  
Morphological Transitions ◽  
Pathogenic Microbes ◽  
Phagosomal Membrane

ABSTRACT For pathogenic microbes to survive ingestion by macrophages, they must subvert powerful microbicidal mechanisms within the phagolysosome. After ingestion, Candida albicans undergoes a morphological transition producing hyphae, while the surrounding phagosome exhibits a loss of phagosomal acidity. However, how these two events are related has remained enigmatic. Now Westman et al. (mBio 9:e01226-18, 2018, https://doi.org/10.1128/mBio.01226-18) report that phagosomal neutralization results from disruption of phagosomal membrane integrity by the enlarging hyphae, directly implicating the morphological transition in physical damage that promotes intracellular survival. The C. albicans intracellular strategy shows parallels with another fungal pathogen, Cryptococcus neoformans, where a morphological changed involving capsular enlargement intracellularly is associated with loss of membrane integrity and death of the host cell. These similarities among distantly related pathogenic fungi suggest that morphological transitions that are common in fungi directly affect the outcome of the fungal cell-macrophage interaction. For this class of organisms, form determines fate in the intracellular environment.

scholarly journals Photoinactivation of catalase sensitizes Candida albicans and Candida auris to ROS-producing agents and immune cells

2021 ◽  
Author(s):  
Pu-Ting Dong ◽  
Yuewei Zhan ◽  
Sebastian Jusuf ◽  
Jie Hui ◽  
Zeina Dagher ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Blue Light ◽  
Optical Switch ◽  
Multidrug Resistant ◽  
Fungal Species ◽  
Candida Auris ◽  
Fungal Cell ◽  
Wide Range ◽  
Inactivation Mechanism ◽  
Macrophage Killing

Nearly all organisms found in nature have evolved and developed their own specific strategies to cope with reactive oxygen species (ROS). Catalase, a heme-containing tetramer protein expressed in a broad range of aerobic fungi, has been utilized as an essential enzymatic ROS detoxifying mechanism, and shows remarkable efficiency in degrading hydrogen peroxide (H2O2) for fungal cell survival and host invasion. Here, we demonstrate that catalase inactivation with blue light renders fungal cells highly susceptible to ROS attack, thus resembling a 'strength-to-weakness optical switch'. To unveil catalase as the underlying molecular target of blue light and its inactivation mechanism, we systematically compared wild-type Candida albicans to a catalase-deficient mutant strain for susceptibility to ROS in the absence/presence of 410 nm treatment. Upon testing on a wide range of fungal species and strains, we found that intracellular catalase could be effectively and universally inactivated by 410 nm blue light. We find that the photoinactivation of catalase in combination with ROS-generating agents is highly effective and potent in achieving full eradication of multiple fungal species and strains, including multiple clinical strains of Candida auris, the causative agent of the global fungal epidemic. In addition, photoinactivation of catalase is shown to facilitate macrophage killing of intracellular Candida albicans. The antifungal efficacy of catalase photoinactivation is further validated using a Candida albicans-induced mouse model of skin abrasion. Taken together, our findings offer a novel catalase-photoinactivation approach to address multidrug-resistant Candida infections.

scholarly journals Efg1 Controls Caspofungin-Induced Cell Aggregation of Candida albicans through the Adhesin Als1

2011 ◽  
Vol 10 (12) ◽  
pp. 1694-1704 ◽  
Author(s):  
Christa Gregori ◽  
Walter Glaser ◽  
Ingrid E. Frohner ◽  
Cristina Reinoso-Martín ◽  
Steffen Rupp ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Cell Aggregation ◽  
Large Cell ◽  
Fungal Species ◽  
Invasive Growth ◽  
Cell Integrity ◽  
Fungal Cell ◽  
Content Type ◽  
Cell Wall Remodeling

ABSTRACTEchinocandin drugs such as caspofungin (CASP), micafungin, and anidulafungin inhibit fungal cell wall biogenesis by blocking Fks1-mediated β-glucan deposition into the cell surface. Candins have become suitable drugs to treat life-threatening diseases caused by several fungal species, includingCandida albicans, that are pathogenic for humans.Here, we present the discovery of a novel CASP-induced flocculation phenotype ofC. albicans, which formed large cell aggregates in the presence of CASP. High concentrations of sugars such as mannose or glucose inhibit CASP-induced flocculation and improve survival ofC. albicanscells exposed to CASP. Notably, exposure ofC. albicanscells to CASP triggers Efg1-dependent expression of the adhesinALS1and induces invasive growth on agar plates. Indeed, cells lacking either Efg1 or Als1 show strongly diminished CASP-induced flocculation, and the absence of Efg1 leads to marked CASP hypersensitivity. On the other hand, CASP-induced invasive growth is enhanced in cells lacking Efg1. Hence, CASP stress drives an Efg1-dependent response, indicating that this multifunctional transcriptional regulator, which is otherwise involved in filamentation, white-to-opaque switching, and virulence, also modulates cell wall remodeling upon CASP challenge. Taken together, our data suggest that CASP-induced cell wall damage activates Efg1 in parallel with the known cell integrity stress signaling pathway to coordinate cell wall remodeling.

scholarly journals A Set of Diverse Genes Influence the Frequency of White-Opaque Switching in Candida albicans

2020 ◽  
Vol 10 (8) ◽  
pp. 2593-2600 ◽  
Author(s):  
Lucas R. Brenes ◽  
Matthew B. Lohse ◽  
Nairi Hartooni ◽  
Alexander D. Johnson
Keyword(s):  
Candida Albicans ◽  
Human Microbiome ◽  
Major Effect ◽  
Fungal Species ◽  
Deletion Mutants ◽  
Genetic Screens ◽  
Cell Functions ◽  
Pheromone Signaling ◽  
Entry Points ◽  
Morphological Transitions

The fungal species Candida albicans is both a member of the human microbiome and a fungal pathogen. C. albicans undergoes several different morphological transitions, including one called white-opaque switching. Here, cells reversibly switch between two states, “white” and “opaque,” and each state is heritable through many cell generations. Each cell type has a distinct cellular and colony morphology and they differ in many other properties including mating, nutritional specialization, and interactions with the innate immune system. Previous genetic screens to gain insight into white-opaque switching have focused on certain classes of genes (for example transcriptional regulators or chromatin modifying enzymes). In this paper, we examined 172 deletion mutants covering a broad range of cell functions. We identified 28 deletion mutants with at least a fivefold effect on switching frequencies; these cover a wide variety of functions ranging from membrane sensors to kinases to proteins of unknown function. In agreement with previous reports, we found that components of the pheromone signaling cascade affect white-to-opaque switching; however, our results suggest that the major effect of Cek1 on white-opaque switching occurs through the cell wall damage response pathway. Most of the genes we identified have not been previously implicated in white-opaque switching and serve as entry points to understand new aspects of this morphological transition.

scholarly journals Global Identification of Biofilm-Specific Proteolysis in Candida albicans

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Michael B. Winter ◽  
Eugenia C. Salcedo ◽  
Matthew B. Lohse ◽  
Nairi Hartooni ◽  
Megha Gulati ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Venous Catheter ◽  
Opportunistic Pathogen ◽  
Fungal Species ◽  
Implanted Medical Devices ◽  
Opportunistic Fungal Pathogen ◽  
Biofilm Development

ABSTRACT Candida albicans is a fungal species that is part of the normal human microbiota and also an opportunistic pathogen capable of causing mucosal and systemic infections. C. albicans cells proliferate in a planktonic (suspension) state, but they also form biofilms, organized and tightly packed communities of cells attached to a solid surface. Biofilms colonize many niches of the human body and persist on implanted medical devices, where they are a major source of new C. albicans infections. Here, we used an unbiased and global substrate-profiling approach to discover proteolytic activities produced specifically by C. albicans biofilms, compared to planktonic cells, with the goal of identifying potential biofilm-specific diagnostic markers and targets for therapeutic intervention. This activity-based profiling approach, coupled with proteomics, identified Sap5 (Candidapepsin-5) and Sap6 (Candidapepsin-6) as major biofilm-specific proteases secreted by C. albicans . Fluorogenic peptide substrates with selectivity for Sap5 or Sap6 confirmed that their activities are highly upregulated in C. albicans biofilms; we also show that these activities are upregulated in other Candida clade pathogens. Deletion of the SAP5 and SAP6 genes in C. albicans compromised biofilm development in vitro in standard biofilm assays and in vivo in a rat central venous catheter biofilm model. This work establishes secreted proteolysis as a promising enzymatic marker and potential therapeutic target for Candida biofilm formation. IMPORTANCE Biofilm formation by the opportunistic fungal pathogen C. albicans is a major cause of life-threatening infections. This work provides a global characterization of secreted proteolytic activity produced specifically by C. albicans biofilms. We identify activity from the proteases Sap5 and Sap6 as highly upregulated during C. albicans biofilm formation and develop Sap-cleavable fluorogenic substrates that enable the detection of biofilms from C. albicans and also from additional pathogenic Candida species. Furthermore, SAP5 and SAP6 deletions confirm that both proteases are required for proper biofilm development in vitro and in vivo . We propose that secreted proteolysis is a promising marker for the diagnosis and potential therapeutic targeting of Candida biofilm-associated infections.

scholarly journals SCREENING, IDENTIFICATION AND ISOLATION OF SOME FUNGAL SPECIES AGAINST OPPORTUNISTIC FUNGAL PATHOGEN CANDIDA ALBICANS

2020 ◽  
Vol 9 (5) ◽  
pp. 2601-2604
Author(s):  
Aakriti Shukla
Keyword(s):  
Candida Albicans ◽  
Heart Valves ◽  
Infectious Agent ◽  
Prescription Medication ◽  
Fungal Species ◽  
Ongoing Research ◽  
Immunocompromised Individual ◽  
Alternative Drug ◽  
Life Threatening ◽  
Opportunistic Fungal Pathogen

Candida albicans or Monilia albicans is an opportunistic fungus, it is basically present on the skin and mucous membranes such like vaginal area, mouth, or rectum part. Candida albicans can travel through the blood and affects intestines, throat, and heart valves of healthy as well as immunocompromised individual. When is there is any change in body temperature Candida albicans becomes an infectious agent and it starting grow out of control it also cause life threating infections to patients with weak immunity (AIDS), patients in ICU and undergoing Chemotherapy. Some of the Candida infections could be treated with home remedies, topical creams or with prescription medication such as clotrimazole, miconazole, nystatin, tioconazole, or oral administration of drugs such as fluconazole and amphotericin B. Although all this antifungal drug helps in getting cure the trouble, but the infection can recur. As per the ongoing research on all over the globe, it has been proven that Candida albicans become resistant over most the drug, so it is necessary to find an alternative drug to cure this life-threatening organism. In the present study we evaluated and screened the secondary metabolites of fungi for the control of Candida albicans by evaluating the potential of fungal bioactive compounds, its purification and characterization.

Antifungal Proteins from Plant Latex

2020 ◽  
Vol 21 (5) ◽  
pp. 497-506
Author(s):  
Mayck Silva Barbosa ◽  
Bruna da Silva Souza ◽  
Ana Clara Silva Sales ◽  
Jhoana D’arc Lopes de Sousa ◽  
Francisca Dayane Soares da Silva ◽  
...  
Keyword(s):  
Cell Walls ◽  
Defense Mechanisms ◽  
Hydrolytic Enzymes ◽  
Fungal Species ◽  
Biologically Active ◽  
Protein Classification ◽  
Fungal Cell ◽  
Antifungal Proteins ◽  
Plant Latex

Latex, a milky fluid found in several plants, is widely used for many purposes, and its proteins have been investigated by researchers. Many studies have shown that latex produced by some plant species is a natural source of biologically active compounds, and many of the hydrolytic enzymes are related to health benefits. Research on the characterization and industrial and pharmaceutical utility of latex has progressed in recent years. Latex proteins are associated with plants’ defense mechanisms, against attacks by fungi. In this respect, there are several biotechnological applications of antifungal proteins. Some findings reveal that antifungal proteins inhibit fungi by interrupting the synthesis of fungal cell walls or rupturing the membrane. Moreover, both phytopathogenic and clinical fungal strains are susceptible to latex proteins. The present review describes some important features of proteins isolated from plant latex which presented in vitro antifungal activities: protein classification, function, molecular weight, isoelectric point, as well as the fungal species that are inhibited by them. We also discuss their mechanisms of action.

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