Open AccessReview
Adaptive Immunity to Cryptococcus neoformans Infections
J. Fungi 2017, 3(4), 64; doi:10.3390/jof3040064 -
Abstract
The Cryptococcus neoformans/Cryptococcus gattii species complex is a group of fungal pathogens with different phenotypic and genotypic diversity that cause disease in immunocompromised patients as well as in healthy individuals. The immune response resulting from the interaction between Cryptococcus and the
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The Cryptococcus neoformans/Cryptococcus gattii species complex is a group of fungal pathogens with different phenotypic and genotypic diversity that cause disease in immunocompromised patients as well as in healthy individuals. The immune response resulting from the interaction between Cryptococcus and the host immune system is a key determinant of the disease outcome. The species C. neoformans causes the majority of human infections, and therefore almost all immunological studies focused on C. neoformans infections. Thus, this review presents current understanding on the role of adaptive immunity during C. neoformans infections both in humans and in animal models of disease. Full article
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Open AccessReview
Function and Biosynthesis of Cell Wall α-1,3-Glucan in Fungi
J. Fungi 2017, 3(4), 63; doi:10.3390/jof3040063 -
Abstract
Although α-1,3-glucan is a major cell wall polysaccharide in filamentous fungi, its biological functions remain unclear, except that it acts as a virulence factor in animal and plant pathogenic fungi: it conceals cell wall β-glucan on the fungal cell surface to circumvent recognition
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Although α-1,3-glucan is a major cell wall polysaccharide in filamentous fungi, its biological functions remain unclear, except that it acts as a virulence factor in animal and plant pathogenic fungi: it conceals cell wall β-glucan on the fungal cell surface to circumvent recognition by hosts. However, cell wall α-1,3-glucan is also present in many of non-pathogenic fungi. Recently, the universal function of α-1,3-glucan as an aggregation factor has been demonstrated. Applications of fungi with modified cell wall α-1,3-glucan in the fermentation industry and of in vitro enzymatically-synthesized α-1,3-glucan in bio-plastics have been developed. This review focuses on the recent progress in our understanding of the biological functions and biosynthetic mechanism of cell wall α-1,3-glucan in fungi. We briefly consider the history of studies on α-1,3-glucan, overview its biological functions and biosynthesis, and finally consider the industrial applications of fungi deficient in α-1,3-glucan. Full article
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Open AccessReview
MCC/Eisosomes Regulate Cell Wall Synthesis and Stress Responses in Fungi
J. Fungi 2017, 3(4), 61; doi:10.3390/jof3040061 -
Abstract
The fungal plasma membrane is critical for cell wall synthesis and other important processes including nutrient uptake, secretion, endocytosis, morphogenesis, and response to stress. To coordinate these diverse functions, the plasma membrane is organized into specialized compartments that vary in size, stability, and
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The fungal plasma membrane is critical for cell wall synthesis and other important processes including nutrient uptake, secretion, endocytosis, morphogenesis, and response to stress. To coordinate these diverse functions, the plasma membrane is organized into specialized compartments that vary in size, stability, and composition. One recently identified domain known as the Membrane Compartment of Can1 (MCC)/eisosome is distinctive in that it corresponds to a furrow-like invagination in the plasma membrane. MCC/eisosomes have been shown to be formed by the Bin/Amphiphysin/Rvs (BAR) domain proteins Lsp1 and Pil1 in a range of fungi. MCC/eisosome domains influence multiple cellular functions; but a very pronounced defect in cell wall synthesis has been observed for mutants with defects in MCC/eisosomes in some yeast species. For example, Candida albicans MCC/eisosome mutants display abnormal spatial regulation of cell wall synthesis, including large invaginations and altered chemical composition of the walls. Recent studies indicate that MCC/eisosomes affect cell wall synthesis in part by regulating the levels of the key regulatory lipid phosphatidylinositol 4,5-bisphosphate (PI4,5P2) in the plasma membrane. One general way MCC/eisosomes function is by acting as protected islands in the plasma membrane, since these domains are very stable. They also act as scaffolds to recruit >20 proteins. Genetic studies aimed at defining the function of the MCC/eisosome proteins have identified important roles in resistance to stress, such as resistance to oxidative stress mediated by the flavodoxin-like proteins Pst1, Pst2, Pst3 and Ycp4. Thus, MCC/eisosomes play multiple roles in plasma membrane organization that protect fungal cells from the environment. Full article
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Open AccessReview
Ecoepidemiology of Cryptococcusgattii in Developing Countries
J. Fungi 2017, 3(4), 62; doi:10.3390/jof3040062 -
Abstract
Cryptococcosis is a systemic infection caused by species of the encapsulated yeast Cryptococcus. The disease may occur in immunocompromised and immunocompetent hosts and is acquired by the inhalation of infectious propagules present in the environment. Cryptococcus is distributed in a plethora of
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Cryptococcosis is a systemic infection caused by species of the encapsulated yeast Cryptococcus. The disease may occur in immunocompromised and immunocompetent hosts and is acquired by the inhalation of infectious propagules present in the environment. Cryptococcus is distributed in a plethora of ecological niches, such as soil, pigeon droppings, and tree hollows, and each year new reservoirs are discovered, which helps researchers to better understand the epidemiology of the disease. In this review, we describe the ecoepidemiology of the C. gattii species complex focusing on clinical cases and ecological reservoirs in developing countries from different continents. We also discuss some important aspects related to the antifungal susceptibility of different species within the C. gattii species complex and bring new insights on the revised Cryptococcus taxonomy. Full article
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Open AccessReview
Innate Immunity to Mucosal Candida Infections
J. Fungi 2017, 3(4), 60; doi:10.3390/jof3040060 -
Abstract
Mucosal epithelial tissues are exposed to high numbers of microbes, including commensal fungi, and are able to distinguish between those that are avirulent and those that cause disease. Epithelial cells have evolved multiple mechanisms to defend against colonization and invasion by Candida species.
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Mucosal epithelial tissues are exposed to high numbers of microbes, including commensal fungi, and are able to distinguish between those that are avirulent and those that cause disease. Epithelial cells have evolved multiple mechanisms to defend against colonization and invasion by Candida species. The interplay between mucosal epithelial tissues and immune cells is key for control and clearance of fungal infections. Our understanding of the mucosal innate host defense system has expanded recently with new studies bringing to light the importance of epithelial cell responses, innate T cells, neutrophils, and other phagocytes during Candida infections. Epithelial tissues release cytokines, host defense peptides, and alarmins during Candida invasion that act in concert to limit fungal proliferation and recruit immune effector cells. The innate T cell/IL-17 axis and recruitment of neutrophils are of central importance in controlling mucosal fungal infections. Here, we review current knowledge of the innate immunity at sites of mucosal Candida infection, with a focus on infections caused by C. albicans. Full article
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Open AccessReview
The PHR Family: The Role of Extracellular Transglycosylases in Shaping Candida albicans Cells
J. Fungi 2017, 3(4), 59; doi:10.3390/jof3040059 -
Abstract
Candida albicans 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 C. albicans to the
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Candida albicans 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 C. albicans 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. The cell wall plays a crucial role in the morphological changes C. albicans undergoes in response to specific environmental cues. Among the different categories of enzymes involved in the formation of the fungal cell wall, the GH72 family of transglycosylases plays an important assembly role. These enzymes cut and religate β-(1,3)-glucan, the major determinant of cell shape. In C. albicans, the PHR family encodes GH72 enzymes, some of which work in specific environmental conditions. In this review, we will summarize the work from the initial discovery of PHR genes to the study of the pH-dependent expression of PHR1 and PHR2, from the characterization of the gene products to the recent findings concerning the stress response generated by the lack of GH72 activity in C. albicans hyphae. Full article
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Open AccessArticle
Fungicidal Activity in the Presence of Keratin as an Important Factor Contributing to In Vivo Efficacy: A Comparison of Efinaconazole, Tavaborole, and Ciclopirox
J. Fungi 2017, 3(4), 58; doi:10.3390/jof3040058 -
Abstract
Use of oral antifungals in the treatment of onychomycosis is commonplace; but their use can be limited by safety and patient concerns. Due to their broader safety margins, topical antifungals (efinaconazole, tavaborole, and ciclopirox) are a useful option in the treatment of mild-to-moderate
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Use of oral antifungals in the treatment of onychomycosis is commonplace; but their use can be limited by safety and patient concerns. Due to their broader safety margins, topical antifungals (efinaconazole, tavaborole, and ciclopirox) are a useful option in the treatment of mild-to-moderate onychomycosis in the USA, but their antifungal activity has yet to be directly compared. This study aims to identify important factors contributing to in vivo efficacies of the three topical antifungals. Minimum inhibitory concentrations (MICs) were determined by Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth microdilution. The MIC90 values of efinaconazole, tavaborole, and ciclopirox for T. rubrum were 0.0078, 8.0, and 0.50 μg/mL, respectively. The MIC90 values for T. mentagrophytes were 0.016, 8.0, and 0.50 μg/mL, respectively. Efinaconazole showed potent fungicidal activity in keratin-containing medium, whereas tavaborole was fungistatic, and ciclopirox not active. In the guinea pig model of onychomycosis, the therapeutic efficacy of efinaconazole was superior to those of tavaborole and ciclopirox. This study suggests that not only fungistatic activity (MIC), but also fungicidal activity in the presence of keratin, is an important factor contributing to the in vivo efficacy of topical antifungal drugs against onychomycosis. Full article
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Open AccessReview
Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision
J. Fungi 2017, 3(4), 57; doi:10.3390/jof3040057 -
Abstract
Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health
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Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health problems including asthma, AIDS, cancer, organ transplantation and corticosteroid therapies. Early accurate diagnosis allows prompt antifungal therapy; however this is often delayed or unavailable leading to death, serious chronic illness or blindness. Recent global estimates have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur annually. Since 2013, the Leading International Fungal Education (LIFE) portal has facilitated the estimation of the burden of serious fungal infections country by country for over 5.7 billion people (>80% of the world’s population). These studies have shown differences in the global burden between countries, within regions of the same country and between at risk populations. Here we interrogate the accuracy of these fungal infection burden estimates in the 43 published papers within the LIFE initiative. Full article
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Open AccessReview
The Human Mucosal Mycobiome and Fungal Community Interactions
J. Fungi 2017, 3(4), 56; doi:10.3390/jof3040056 -
Abstract
With the advent of high-throughput sequencing techniques, the astonishing extent and complexity of the microbial communities that reside within and upon us has begun to become clear. Moreover, with advances in computing and modelling methods, we are now beginning to grasp just how
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With the advent of high-throughput sequencing techniques, the astonishing extent and complexity of the microbial communities that reside within and upon us has begun to become clear. Moreover, with advances in computing and modelling methods, we are now beginning to grasp just how dynamic our interactions with these communities are. The diversity of both these communities and their interactions—both within the community and with us—are dependent on a multitude of factors, both microbial- and host-mediated. Importantly, it is becoming clear that shifts in the makeup of these communities, or their responses, are linked to different disease states. Although much of the work to define these interactions and links has been investigating bacterial communities, recently there has been significant growth in the body of knowledge, indicating that shifts in the host fungal communities (mycobiome) are also intimately linked to disease status. In this review, we will explore these associations, along with the interactions between fungal communities and their human and microbial habitat, and discuss the future applications of systems biology in determining their role in disease status. Full article
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Open AccessReview
The Multifaceted Role of T-Helper Responses in Host Defense against Aspergillus fumigatus
J. Fungi 2017, 3(4), 55; doi:10.3390/jof3040055 -
Abstract
The ubiquitous opportunistic fungal pathogen Aspergillus fumigatus rarely causes infections in immunocompetent individuals. A healthy functional innate immune system plays a crucial role in preventing Aspergillus-infection. This pivotal role for the innate immune system makes it a main research focus in studying
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The ubiquitous opportunistic fungal pathogen Aspergillus fumigatus rarely causes infections in immunocompetent individuals. A healthy functional innate immune system plays a crucial role in preventing Aspergillus-infection. This pivotal role for the innate immune system makes it a main research focus in studying the pathogenesis of aspergillosis. Although sometimes overshadowed by the innate immune response, the adaptive immune response, and in particular T-helper responses, also represents a key player in host defense against Aspergillus. Virtually all T-helper subsets have been described to play a role during aspergillosis, with the Th1 response being crucial for fungal clearance. However; morbidity and mortality of aspergillosis can also be partly attributed to detrimental immune responses resulting from adaptive immune activation. Th2 responses benefit fungal persistence; and are the foundation of allergic forms of aspergillosis. The Th17 response has two sides; although crucial for granulocyte recruitment, it can be involved in detrimental immunopathology. Regulatory T-cells, the endogenous regulators of inflammatory responses, play a key role in controlling detrimental inflammatory responses during aspergillosis. The current knowledge of the adaptive immune response against A. fumigatus is summarized in this review. A better understanding on how T-helper responses facilitate clearance of Aspergillus-infection and control inflammation can be the fundamental basis for understanding the pathogenesis of aspergillosis and for the development of novel host-directed therapies. Full article
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Open AccessReview
Cryptococcus–Epithelial Interactions
J. Fungi 2017, 3(4), 53; doi:10.3390/jof3040053 -
Abstract
The fungal pathogen, Cryptococcus neoformans, causes devastating levels of morbidity and mortality. Infections with this fungus tend to be predominantly in immunocompromised individuals, such as those with HIV. Infections initiate with inhalation of cryptococcal cells and entry of the pathogen into the
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The fungal pathogen, Cryptococcus neoformans, causes devastating levels of morbidity and mortality. Infections with this fungus tend to be predominantly in immunocompromised individuals, such as those with HIV. Infections initiate with inhalation of cryptococcal cells and entry of the pathogen into the lungs. The bronchial epithelial cells of the upper airway and the alveolar epithelial cells of the lower airway are likely to be the first host cells that Cryptococcus engage with. Thus the interaction of cryptococci and the respiratory epithelia will be the focus of this review. C. neoformans has been shown to adhere to respiratory epithelial cells, although if the role of the capsule is in aiding or hindering this adhesion is debatable. The epithelia are also able to react to cryptococci with the release of cytokines and chemokines to start the immune response to this invading pathogen. The activity of surfactant components that line this mucosal barrier towards Cryptococcus and the metabolic and transcriptional reaction of cryptococci when encountering epithelial cells will also be discussed. Full article
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Open AccessArticle
A Novel Assay Reveals a Maturation Process during Ascospore Wall Formation
J. Fungi 2017, 3(4), 54; doi:10.3390/jof3040054 -
Abstract
The ascospore wall of the budding yeast Saccharomyces cerevisiae consists of inner layers of similar composition to the vegetative cell wall and outer layers made of spore-specific components that confer increased stress resistance on the spore. The primary constituents of the outer spore
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The ascospore wall of the budding yeast Saccharomyces cerevisiae consists of inner layers of similar composition to the vegetative cell wall and outer layers made of spore-specific components that confer increased stress resistance on the spore. The primary constituents of the outer spore wall are chitosan, dityrosine, and a third component termed Chi that has been identified by spectrometry but whose chemical structure is not known. The lipophilic dye monodansylpentane readily stains lipid droplets inside of newly formed ascospores but, over the course of several days, the spores become impermeable to the dye. The generation of this permeability barrier requires the chitosan layer, but not dityrosine layer, of the spore wall. Screening of a set of mutants with different outer spore wall defects reveals that impermeability to the dye requires not just the presence of chitosan, but another factor as well, possibly Chi, and suggests that the OSW2 gene product is required for synthesis of this factor. Testing of mutants that block synthesis of specific aromatic amino acids indicates that de novo synthesis of tyrosine contributes not only to formation of the dityrosine layer but to impermeability of the wall as well, suggesting a second role for aromatic amino acids in spore wall synthesis. Full article
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Open AccessReview
The Role of IL-17 in Protection against Mucosal Candida Infections
J. Fungi 2017, 3(4), 52; doi:10.3390/jof3040052 -
Abstract
Interleukin-17 (IL-17) is a proinflammatory cytokine produced by adaptive CD4+ T helper cells and innate lymphocytes, such as γδ-T cells and TCRβ+ “natural” Th17 cells. IL-17 activates signaling through the IL-17 receptor, which induces other proinflammatory cytokines, antimicrobial peptides and neutrophil chemokines that
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Interleukin-17 (IL-17) is a proinflammatory cytokine produced by adaptive CD4+ T helper cells and innate lymphocytes, such as γδ-T cells and TCRβ+ “natural” Th17 cells. IL-17 activates signaling through the IL-17 receptor, which induces other proinflammatory cytokines, antimicrobial peptides and neutrophil chemokines that are important for antifungal activity. The importance of IL-17 in protective antifungal immunity is evident in mice and humans, where various genetic defects related to the IL-17-signaling pathway render them highly susceptible to forms of candidiasis such oropharyngeal candidiasis (OPC) or more broadly chronic mucocutaneous candidiasis (CMC), both caused mainly by the opportunistic fungal pathogen Candida albicans. OPC is common in infants and the elderly, HIV/AIDS and patients receiving chemotherapy and/or radiotherapy for head and neck cancers. This review focuses on the role of IL-17 in protection against candidiasis, and includes a brief discussion of non-Candida albicans fungal infections, as well as how therapeutic interventions blocking IL-17-related components can affect antifungal immunity. Full article
Open AccessReview
Fungal Strategies to Evade the Host Immune Recognition
J. Fungi 2017, 3(4), 51; doi:10.3390/jof3040051 -
Abstract
The recognition of fungal cells by the host immune system is key during the establishment of a protective anti-fungal response. Even though the immune system has evolved a vast number of processes to control these organisms, they have developed strategies to fight back,
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The recognition of fungal cells by the host immune system is key during the establishment of a protective anti-fungal response. Even though the immune system has evolved a vast number of processes to control these organisms, they have developed strategies to fight back, avoiding the proper recognition by immune components and thus interfering with the host protective mechanisms. Therefore, the strategies to evade the immune system are as important as the virulence factors and attributes that damage the host tissues and cells. Here, we performed a thorough revision of the main fungal tactics to escape from the host immunosurveillance processes. These include the composition and organization of the cell wall, the fungal capsule, the formation of titan cells, biofilms, and asteroid bodies; the ability to undergo dimorphism; and the escape from nutritional immunity, extracellular traps, phagocytosis, and the action of humoral immune effectors. Full article
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Open AccessArticle
Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole
J. Fungi 2017, 3(3), 50; doi:10.3390/jof3030050 -
Abstract
The paucity of effective antifungals against Aspergillus and increasing resistance, the recognition of the importance of Aspergillus biofilm in several clinical settings, and reports of verapamil—a calcium channel blocker—efficacy against Candida biofilm and hyphal growth, and synergy with an azole antifungal in vitro,
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The paucity of effective antifungals against Aspergillus and increasing resistance, the recognition of the importance of Aspergillus biofilm in several clinical settings, and reports of verapamil—a calcium channel blocker—efficacy against Candida biofilm and hyphal growth, and synergy with an azole antifungal in vitro, led to a study of verapamil ± voriconazole against Aspergillus. Broth macrodilution methodology was utilized for MIC (minimum inhibitory concentration) and MFC (minimum fungicidal concentration) determination. The metabolic effects (assessed by XTT [2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt]) on biofilm formation by conidia were studied upon exposure to verapamil, verapamil plus voriconazole, or voriconazole alone. For biofilm formation, we found less inhibition from the combinations than with either drug alone, or less inhibition from the combination than that of the more potent drug alone. For preformed biofilm, we found no significant change in activity comparing voriconazole alone compared to added verapamil, and no significant alteration of activity of the more potent voriconazole, at any concentration in the range tested, by addition of a concentration of verapamil that is inhibitory alone. In full checkerboard assays with planktonic fungus, there was no indication of any effect of one drug on the other (indifference). Although verapamil was similarly inactive against planktonic Aspergillus, as with Candida, verapamil was indeed active against Aspergillus biofilm. However, indifference and antagonism was found with voriconazole. Full article
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Open AccessFeature PaperArticle
Conserved Inhibition of Neutrophil Extracellular Trap Release by Clinical Candida albicans Biofilms
J. Fungi 2017, 3(3), 49; doi:10.3390/jof3030049 -
Abstract
Candida albicans biofilms are difficult to eradicate due to their resistance to host defenses and antifungal drugs. Although neutrophils are the primary responder to C. albicans during invasive candidiasis, biofilms resist killing by neutrophils. Prior investigation, with the commonly used laboratory strain SC5314,
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Candida albicans biofilms are difficult to eradicate due to their resistance to host defenses and antifungal drugs. Although neutrophils are the primary responder to C. albicans during invasive candidiasis, biofilms resist killing by neutrophils. Prior investigation, with the commonly used laboratory strain SC5314, linked this phenotype to the impaired release of neutrophil extracellular traps (NETs), which are structures of DNA, histones, and antimicrobial proteins involved in extracellular microbial killing. Considering the diversity of C. albicans biofilms, we examined the neutrophil response to a subset of clinical isolates forming biofilms with varying depths and architectures. Using fluorescent staining of DNA and scanning electron microscopy, we found that inhibition of NET release was conserved across the clinical isolates. However, the dampening of the production of reactive oxygen species (ROS) by neutrophils was strain-dependent, suggesting an uncoupling of ROS and NET inhibition. Our findings show that biofilms formed by clinical C. albicans isolates uniformly impair the release of NETs. Further investigation of this pathway may reveal novel approaches to augment immunity to C. albicans biofilm infections. Full article
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Open AccessFeature PaperReview
Innate and Adaptive Immunity to Mucorales
J. Fungi 2017, 3(3), 48; doi:10.3390/jof3030048 -
Abstract
Mucormycosis is an invasive fungal infection characterised by rapid filamentous growth, which leads to angioinvasion, thrombosis, and tissue necrosis. The high mortality rates (50–100%) associated with mucormycosis are reflective of not only the aggressive nature of the infection and the poor therapeutics currently
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Mucormycosis is an invasive fungal infection characterised by rapid filamentous growth, which leads to angioinvasion, thrombosis, and tissue necrosis. The high mortality rates (50–100%) associated with mucormycosis are reflective of not only the aggressive nature of the infection and the poor therapeutics currently employed, but also the failure of the human immune system to successfully clear the infection. Immune effector interaction with Mucorales is influenced by the developmental stage of the mucormycete spore. In a healthy immune environment, resting spores are resistant to phagocytic killing. Contrarily, swollen spores and hyphae are susceptible to damage and degradation by macrophages and neutrophils. Under the effects of immune suppression, the recruitment and efficacy of macrophage and neutrophil activity against mucormycetes is considerably reduced. Following penetration of the endothelial lining, Mucorales encounter platelets. Platelets adhere to both mucormycete spores and hyphae, and exhibit germination suppression and hyphal damage capacity in vitro. Dendritic cells are activated in response to Mucorales hyphae only, and induce adaptive immunity. It is crucial to further knowledge regarding our immune system’s failure to eradicate resting spores under intact immunity and inhibit fungal growth under immunocompromised conditions, in order to understand mucormycosis pathogenicity and enhance therapeutic strategies for mucormycosis. Full article
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Open AccessFeature PaperReview
Immune Recognition of Fungal Polysaccharides
J. Fungi 2017, 3(3), 47; doi:10.3390/jof3030047 -
Abstract
The incidence of fungal infections has dramatically increased in recent years, in large part due to increased use of immunosuppressive medications, as well as aggressive medical and surgical interventions that compromise natural skin and mucosal barriers. There are relatively few currently licensed antifungal
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The incidence of fungal infections has dramatically increased in recent years, in large part due to increased use of immunosuppressive medications, as well as aggressive medical and surgical interventions that compromise natural skin and mucosal barriers. There are relatively few currently licensed antifungal drugs, and rising resistance to these agents has led to interest in the development of novel preventative and therapeutic strategies targeting these devastating infections. One approach to combat fungal infections is to augment the host immune response towards these organisms. The polysaccharide-rich cell wall is the initial point of contact between fungi and the host immune system, and therefore, represents an important target for immunotherapeutic approaches. This review highlights the advances made in our understanding of the mechanisms by which the immune system recognizes and interacts with exopolysaccharides produced by four of the most common fungal pathogens: Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, and Histoplasma capsulatum. Work to date suggests that inner cell wall polysaccharides that play an important structural role are the most conserved across diverse members of the fungal kingdom, and elicit the strongest innate immune responses. The immune system senses these carbohydrates through receptors, such as lectins and complement proteins. In contrast, a greater diversity of polysaccharides is found within the outer cell walls of pathogenic fungi. These glycans play an important role in immune evasion, and can even induce anti-inflammatory host responses. Further study of the complex interactions between the host immune system and the fungal polysaccharides will be necessary to develop more effective therapeutic strategies, as well as to explore the use of immunosuppressive polysaccharides as therapeutic agents to modulate inflammation. Full article
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Open AccessReview
Natural Antimicrobial Peptides as Inspiration for Design of a New Generation Antifungal Compounds
J. Fungi 2017, 3(3), 46; doi:10.3390/jof3030046 -
Abstract
Invasive fungal infections are associated with high mortality rates, despite appropriate antifungal therapy. Limited therapeutic options, resistance development and the high mortality of invasive fungal infections brought about more concern triggering the search for new compounds capable of interfering with fungal viability and
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Invasive fungal infections are associated with high mortality rates, despite appropriate antifungal therapy. Limited therapeutic options, resistance development and the high mortality of invasive fungal infections brought about more concern triggering the search for new compounds capable of interfering with fungal viability and virulence. In this context, peptides gained attention as promising candidates for the antimycotics development. Variety of structural and functional characteristics identified for various natural antifungal peptides makes them excellent starting points for design novel drug candidates. Current review provides a brief overview of natural and synthetic antifungal peptides. Full article
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Open AccessEditorial
Fungal Pigments: Deep into the Rainbow of Colorful Fungi
J. Fungi 2017, 3(3), 45; doi:10.3390/jof3030045 -
Abstract
With the impact of globalization on research trends, the search for healthier life styles, the increasing public demand for natural, organic, and ”clean labelled” products, as well as the growing global market for natural colorants in economically fast-growing countries all over the world,
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With the impact of globalization on research trends, the search for healthier life styles, the increasing public demand for natural, organic, and ”clean labelled” products, as well as the growing global market for natural colorants in economically fast-growing countries all over the world, filamentous fungi started to be investigated as readily available sources of chemically diverse pigments and colorants.[...] Full article