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J. Fungi, Volume 4, Issue 4 (December 2018) – 28 articles

Cover Story (view full-size image): The human oral cavity normally harbors hundreds of species of microorganisms, which are often organized as multi-species biofilms. Interkingdom interactions within oral microbiota, such as those established between fungi and bacteria, affect health and disease and are of increasing interest. In this review article, we list and describe some of the better characterized synergistic and antagonistic interactions between Candida species, with special emphasis on C. albicans, and oral bacteria. View this paper.
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18 pages, 1947 KiB  
Review
Development and Applications of Prognostic Risk Models in the Management of Invasive Mold Disease
by Marta Stanzani and Russell E. Lewis
J. Fungi 2018, 4(4), 141; https://doi.org/10.3390/jof4040141 - 19 Dec 2018
Cited by 7 | Viewed by 3488
Abstract
Prognostic models or risk scores are frequently used to aid individualize risk assessment for diseases with multiple, complex risk factors and diagnostic challenges. However, relatively little attention has been paid to the development of risk models for invasive mold diseases encountered in patients [...] Read more.
Prognostic models or risk scores are frequently used to aid individualize risk assessment for diseases with multiple, complex risk factors and diagnostic challenges. However, relatively little attention has been paid to the development of risk models for invasive mold diseases encountered in patients with hematological malignancies, despite a large body of epidemiological research. Herein we review recent studies that have described the development of prognostic models for mold disease, summarize our experience with the development and clinical use of one such model (BOSCORE), and discuss the potential impact of prognostic risk scores for individualized therapy, diagnostic and antifungal stewardship, as well as clinical and epidemiological research. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
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18 pages, 1169 KiB  
Review
The Significance of Lipids to Biofilm Formation in Candida albicans: An Emerging Perspective
by Darakshan Alim, Shabnam Sircaik and Sneh Lata Panwar
J. Fungi 2018, 4(4), 140; https://doi.org/10.3390/jof4040140 - 18 Dec 2018
Cited by 41 | Viewed by 11463
Abstract
Candida albicans, 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 [...] Read more.
Candida albicans, 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 C. albicans. Lipids modulate mixed species biofilm formation in vivo and inherent antifungal resistance associated with these organized communities. Cells in C. albicans biofilms display phase-dependent changes in phospholipid classes and in levels of lipid raft formation. Systematic studies with genetically modified strains in which the membrane phospholipid composition can be manipulated are limited in C. albicans. In this review, we summarize the knowledge accumulated on the impact that alterations in phospholipids may have on the biofilm forming ability of C. albicans in the human host. This review may provide the requisite impetus to analyze lipids from a therapeutic standpoint in managing C. albicans biofilms. Full article
(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)
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22 pages, 1972 KiB  
Review
Understanding Pathogenesis and Care Challenges of Immune Reconstitution Inflammatory Syndrome in Fungal Infections
by Sarah Dellière, Romain Guery, Sophie Candon, Blandine Rammaert, Claire Aguilar, Fanny Lanternier, Lucienne Chatenoud and Olivier Lortholary
J. Fungi 2018, 4(4), 139; https://doi.org/10.3390/jof4040139 - 17 Dec 2018
Cited by 36 | Viewed by 5425
Abstract
Immune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune [...] Read more.
Immune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune reconstitution inflammatory syndrome (IRIS), which causes significant mortality and morbidity. Fungal-associated IRIS raises several diagnostic and management issues. Mostly studied with Cryptococcus, it has also been described with other major fungi implicated in human invasive fungal infections, such as Pneumocystis, Aspergillus, Candida, and Histoplasma. Furthermore, the understanding of IRIS pathogenesis remains in its infancy. This review summarizes current knowledge regarding the clinical characteristics of IRIS depending on fungal species and existing strategies to predict, prevent, and treat IRIS in this patient population, and tries to propose a common immunological background to fungal IRIS. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
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15 pages, 312 KiB  
Review
From the Clinical Mycology Laboratory: New Species and Changes in Fungal Taxonomy and Nomenclature
by Nathan P. Wiederhold and Connie F. C. Gibas
J. Fungi 2018, 4(4), 138; https://doi.org/10.3390/jof4040138 - 16 Dec 2018
Cited by 12 | Viewed by 6121
Abstract
Fungal taxonomy is the branch of mycology by which we classify and group fungi based on similarities or differences. Historically, this was done by morphologic characteristics and other phenotypic traits. However, with the advent of the molecular age in mycology, phylogenetic analysis based [...] Read more.
Fungal taxonomy is the branch of mycology by which we classify and group fungi based on similarities or differences. Historically, this was done by morphologic characteristics and other phenotypic traits. However, with the advent of the molecular age in mycology, phylogenetic analysis based on DNA sequences has replaced these classic means for grouping related species. This, along with the abandonment of the dual nomenclature system, has led to a marked increase in the number of new species and reclassification of known species. Although these evaluations and changes are necessary to move the field forward, there is concern among medical mycologists that the rapidity by which fungal nomenclature is changing could cause confusion in the clinical literature. Thus, there is a proposal to allow medical mycologists to adopt changes in taxonomy and nomenclature at a slower pace. In this review, changes in the taxonomy and nomenclature of medically relevant fungi will be discussed along with the impact this may have on clinicians and patient care. Specific examples of changes and current controversies will also be given. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
17 pages, 869 KiB  
Review
Immunomodulation as a Therapy for Aspergillus Infection: Current Status and Future Perspectives
by Chris D. Lauruschkat, Hermann Einsele and Juergen Loeffler
J. Fungi 2018, 4(4), 137; https://doi.org/10.3390/jof4040137 - 14 Dec 2018
Cited by 22 | Viewed by 5933
Abstract
Invasive aspergillosis (IA) is the most serious life-threatening infectious complication of intensive remission induction chemotherapy and allogeneic stem cell transplantation in patients with a variety of hematological malignancies. Aspergillus fumigatus is the most commonly isolated species from cases of IA. Despite the various [...] Read more.
Invasive aspergillosis (IA) is the most serious life-threatening infectious complication of intensive remission induction chemotherapy and allogeneic stem cell transplantation in patients with a variety of hematological malignancies. Aspergillus fumigatus is the most commonly isolated species from cases of IA. Despite the various improvements that have been made with preventative strategies and the development of antifungal drugs, there is an urgent need for new therapeutic approaches that focus on strategies to boost the host’s immune response, since immunological recovery is recognized as being the major determinant of the outcome of IA. Here, we aim to summarize current knowledge about a broad variety of immunotherapeutic approaches against IA, including therapies based on the transfer of distinct immune cell populations, and the administration of cytokines and antibodies. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
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26 pages, 1270 KiB  
Review
The Zebrafish as a Model Host for Invasive Fungal Infections
by Emily E. Rosowski, Benjamin P. Knox, Linda S. Archambault, Anna Huttenlocher, Nancy P. Keller, Robert T. Wheeler and J. Muse Davis
J. Fungi 2018, 4(4), 136; https://doi.org/10.3390/jof4040136 - 13 Dec 2018
Cited by 42 | Viewed by 8861
Abstract
The zebrafish has become a widely accepted model host for studies of infectious disease, including fungal infections. The species is genetically tractable, and the larvae are transparent and amenable to prolonged in vivo imaging and small molecule screening. The aim of this review [...] Read more.
The zebrafish has become a widely accepted model host for studies of infectious disease, including fungal infections. The species is genetically tractable, and the larvae are transparent and amenable to prolonged in vivo imaging and small molecule screening. The aim of this review is to provide a thorough introduction into the published studies of fungal infection in the zebrafish and the specific ways in which this model has benefited the field. In doing so, we hope to provide potential new zebrafish researchers with a snapshot of the current toolbox and prior results, while illustrating how the model has been used well and where the unfulfilled potential of this model can be found. Full article
(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)
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3 pages, 163 KiB  
Editorial
Special Issue: Treatments for Fungal Infections
by Esther Segal and Daniel Elad
J. Fungi 2018, 4(4), 135; https://doi.org/10.3390/jof4040135 - 12 Dec 2018
Cited by 6 | Viewed by 3107
Abstract
Antifungal therapy is complicated compared to antibacterial treatments by the fact that fungi and their hosts are both eukaryotic organisms, resulting in fewer targets for selective activity. [...] Full article
(This article belongs to the Special Issue Treatments for Fungal Infections)
14 pages, 3241 KiB  
Article
Anti-Candida albicans Activity of Thiazolylhydrazone Derivatives in Invertebrate and Murine Models
by Lana Ivone Barreto Cruz, Larissa Ferreira Finamore Lopes, Felipe De Camargo Ribeiro, Nívea Pereira De Sá, Cleudiomar Inácio Lino, Nagendran Tharmalingam, Renata Barbosa De Oliveira, Carlos Augusto Rosa, Eleftherios Mylonakis, Beth Burgwyn Fuchs and Susana Johann
J. Fungi 2018, 4(4), 134; https://doi.org/10.3390/jof4040134 - 12 Dec 2018
Cited by 15 | Viewed by 3825
Abstract
Candidiasis is an opportunistic fungal infection with Candida albicans being the most frequently isolated species. Treatment of these infections is challenging due to resistance that can develop during therapy, and the limited number of available antifungal compounds. Given this situation, the aim of [...] Read more.
Candidiasis is an opportunistic fungal infection with Candida albicans being the most frequently isolated species. Treatment of these infections is challenging due to resistance that can develop during therapy, and the limited number of available antifungal compounds. Given this situation, the aim of this study was to evaluate the antifungal activity of four thiazolylhydrazone compounds against C. albicans. Thiazolylhydrazone compounds 1, 2, 3, and 4 were found to exert antifungal activity, with MICs of 0.125–16.0 μg/mL against C. albicans. The toxicity of the compounds was evaluated using human erythrocytes and yielded LC50 > 64 μg/mL. The compounds were further evaluated using the greater wax moth Galleria mellonella as an in vivo model. The compounds prolonged larval survival when tested between 5 and 15 mg/kg, performing as well as fluconazole. Compound 2 was evaluated in murine models of oral and systemic candidiasis. In the oral model, compound 2 reduced the fungal load on the mouse tongue; and in the systemic model it reduced the fungal burden found in the kidney when tested at 10 mg/kg. These results show that thiazolylhydrazones are an antifungal towards C. albicans with in vivo efficacy. Full article
(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)
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22 pages, 307 KiB  
Review
Pre-Existing Liver Disease and Toxicity of Antifungals
by Nikolaos Spernovasilis and Diamantis P. Kofteridis
J. Fungi 2018, 4(4), 133; https://doi.org/10.3390/jof4040133 - 10 Dec 2018
Cited by 28 | Viewed by 13781
Abstract
Pre-existing liver disease in patients with invasive fungal infections further complicates their management. Altered pharmacokinetics and tolerance issues of antifungal drugs are important concerns. Adjustment of the dosage of antifungal agents in these cases can be challenging given that current evidence to guide [...] Read more.
Pre-existing liver disease in patients with invasive fungal infections further complicates their management. Altered pharmacokinetics and tolerance issues of antifungal drugs are important concerns. Adjustment of the dosage of antifungal agents in these cases can be challenging given that current evidence to guide decision-making is limited. This comprehensive review aims to evaluate the existing evidence related to antifungal treatment in individuals with liver dysfunction. This article also provides suggestions for dosage adjustment of antifungal drugs in patients with varying degrees of hepatic impairment, after accounting for established or emerging pharmacokinetic–pharmacodynamic relationships with regard to antifungal drug efficacy in vivo. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
10 pages, 1364 KiB  
Review
Going with the Flo: The Role of Flo11-Dependent and Independent Interactions in Yeast Mat Formation
by Todd B. Reynolds
J. Fungi 2018, 4(4), 132; https://doi.org/10.3390/jof4040132 - 07 Dec 2018
Cited by 12 | Viewed by 5460
Abstract
Strains of the bakers’ yeast Saccharomyces cerevisiae that are able to generate a multicellular structure called a mat on low percentage (0.3%) agar plates are given a selective advantage over strains that cannot exhibit this phenotype. This environment may exhibit some similarities to [...] Read more.
Strains of the bakers’ yeast Saccharomyces cerevisiae that are able to generate a multicellular structure called a mat on low percentage (0.3%) agar plates are given a selective advantage over strains that cannot exhibit this phenotype. This environment may exhibit some similarities to the rotting fruit on which S. cerevisiae often grows in nature. Mat formation occurs when the cells spread over the plate as they grow, and cells in the center of the biofilm aggregate to form multicellular structures that resemble a floral pattern. This multicellular behavior is dependent on the cell surface flocculin Flo11. This review covers recent information on the structure of Flo11 and how this likely impacts mat formation as well as how variegated expression of Flo11 influences mat formation. Finally, it also discusses several Flo11-independent genetic factors that control mat formation, such as vacuolar protein sorting (VPS) genes, cell wall signaling components, and heat shock proteins. Full article
(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)
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8 pages, 232 KiB  
Article
Environmental Isolates of Multi-Azole-Resistant Aspergillus spp. in Southern Italy
by Laura Trovato, Guido Scalia, Maria Domina and Salvatore Oliveri
J. Fungi 2018, 4(4), 131; https://doi.org/10.3390/jof4040131 - 06 Dec 2018
Cited by 12 | Viewed by 3036
Abstract
Azole resistance in Aspergillus spp. has been increasingly reported worldwide. Acquired azole resistance is probably linked to environmental exposure to fungicides used in agriculture. We collected a total of 84 soil and leaf samples from eight farms in Southern Italy. Aspergillus isolates were [...] Read more.
Azole resistance in Aspergillus spp. has been increasingly reported worldwide. Acquired azole resistance is probably linked to environmental exposure to fungicides used in agriculture. We collected a total of 84 soil and leaf samples from eight farms in Southern Italy. Aspergillus isolates were tested for resistance to itraconazole, posaconazole, and voriconazole by the EUCAST method. Five out of 84 samples yielded A. fumigatus isolates: four of them were itraconazole-resistant and were identified as A. fumigatus sensu stricto, three of them were posaconazole-resistant, and two were also voriconazole-resistant. All three isolates harbored the TR34/L98H resistance mechanism, which was detected by DNA sequencing of the cyp51A gene. Fifteen out of 84 samples yielded Aspergillus spp. isolates and included 11 itraconazole-resistant isolates: Aspergillus section Nigri (9) and Aspergillus section Flavi (2). Our study reports for the first time the isolation of azole-resistant A. fumigatus harboring TR34/L98H mutation from the environment of Southern Italy. The present work provides a better understanding of the magnitude of the environmental spread of azole resistance in the context of a necessary effective surveillance program to improve the management of Aspergillus-related disease. Full article
10 pages, 1432 KiB  
Review
Chemical Diversity and Biological Activities of Phaeosphaeria Fungi Genus: A Systematic Review
by Amr El-Demerdash
J. Fungi 2018, 4(4), 130; https://doi.org/10.3390/jof4040130 - 05 Dec 2018
Cited by 15 | Viewed by 4096
Abstract
Microbial natural products (MNPs) have been identified as important hotspots and effective sources for drug lead discovery. The genus Phaeosphaeria (family: Phaeosphaeriaceae, order: Pleosporales), in particular, has produced divergent chemical structures, including pyrazine alkaloids, isocoumarins, perylenequinones, anthraquinones, diterpenes, and cyclic peptides, which display [...] Read more.
Microbial natural products (MNPs) have been identified as important hotspots and effective sources for drug lead discovery. The genus Phaeosphaeria (family: Phaeosphaeriaceae, order: Pleosporales), in particular, has produced divergent chemical structures, including pyrazine alkaloids, isocoumarins, perylenequinones, anthraquinones, diterpenes, and cyclic peptides, which display a wide scope of biological potentialities. This contribution comprehensively highlights, over the period 1974–2018, the chemistry and biology of the isolated natural products from the micro-filamentous Phaeosphaeria fungi genus. A list of 71 compounds, with structural and biological diversities, were gathered into 5 main groups. Full article
(This article belongs to the Special Issue Fungal Polyketides and Other Secondary Metabolites)
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13 pages, 272 KiB  
Review
Antifungal Resistance: Specific Focus on Multidrug Resistance in Candida auris and Secondary Azole Resistance in Aspergillus fumigatus
by Sevtap Arikan-Akdagli, Mahmoud Ghannoum and Jacques F. Meis
J. Fungi 2018, 4(4), 129; https://doi.org/10.3390/jof4040129 - 05 Dec 2018
Cited by 35 | Viewed by 5799
Abstract
Antifungal resistance is a topic of concern, particularly for specific fungal species and drugs. Among these are the multidrug-resistant Candida auris and azole-resistant Aspergillus fumigatus. While the knowledge on molecular mechanisms of resistance is now accumulating, further data are also available for [...] Read more.
Antifungal resistance is a topic of concern, particularly for specific fungal species and drugs. Among these are the multidrug-resistant Candida auris and azole-resistant Aspergillus fumigatus. While the knowledge on molecular mechanisms of resistance is now accumulating, further data are also available for the clinical implications and the extent of correlation of in vitro resistance to clinical outcomes. This review article summarizes the epidemiology of C. auris infections, animal models focusing on the activity of novel antifungal compounds in C. auris infections, virulence factors, and the mechanisms of antifungal resistance for this multi-resistant Candida species. Regarding A. fumigatus, the significance of azoles in the treatment of A. fumigatus infections, reference methods available for the detection of resistance in vitro, molecular mechanisms of secondary azole resistance, routes of acquisition, and clinical implications of in vitro resistance are covered to provide guidance for the current status of azole resistance in A. fumigatus. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts)
19 pages, 1296 KiB  
Review
Recent Advances in the Use of Galleria mellonella Model to Study Immune Responses against Human Pathogens
by Thais Cristine Pereira, Patrícia Pimentel De Barros, Luciana Ruano de Oliveira Fugisaki, Rodnei Dennis Rossoni, Felipe de Camargo Ribeiro, Raquel Teles De Menezes, Juliana Campos Junqueira and Liliana Scorzoni
J. Fungi 2018, 4(4), 128; https://doi.org/10.3390/jof4040128 - 27 Nov 2018
Cited by 109 | Viewed by 8762
Abstract
The use of invertebrates for in vivo studies in microbiology is well established in the scientific community. Larvae of Galleria mellonella are a widely used model for studying pathogenesis, the efficacy of new antimicrobial compounds, and immune responses. The immune system of G. [...] Read more.
The use of invertebrates for in vivo studies in microbiology is well established in the scientific community. Larvae of Galleria mellonella are a widely used model for studying pathogenesis, the efficacy of new antimicrobial compounds, and immune responses. The immune system of G. mellonella larvae is structurally and functionally similar to the innate immune response of mammals, which makes this model suitable for such studies. In this review, cellular responses (hemocytes activity: phagocytosis, nodulation, and encapsulation) and humoral responses (reactions or soluble molecules released in the hemolymph as antimicrobial peptides, melanization, clotting, free radical production, and primary immunization) are discussed, highlighting the use of G. mellonella as a model of immune response to different human pathogenic microorganisms. Full article
(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)
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29 pages, 697 KiB  
Review
Therapy and Management of Pneumocystis jirovecii Infection
by P. Lewis White, Jessica S. Price and Matthijs Backx
J. Fungi 2018, 4(4), 127; https://doi.org/10.3390/jof4040127 - 22 Nov 2018
Cited by 44 | Viewed by 12693
Abstract
The rates of Pneumocystis pneumonia (PcP) are increasing in the HIV-negative susceptible population. Guidance for the prophylaxis and treatment of PcP in HIV, haematology, and solid-organ transplant (SOT) recipients is available, although for many other populations (e.g., auto-immune disorders) there remains an urgent [...] Read more.
The rates of Pneumocystis pneumonia (PcP) are increasing in the HIV-negative susceptible population. Guidance for the prophylaxis and treatment of PcP in HIV, haematology, and solid-organ transplant (SOT) recipients is available, although for many other populations (e.g., auto-immune disorders) there remains an urgent need for recommendations. The main drug for both prophylaxis and treatment of PcP is trimethoprim/sulfamethoxazole, but resistance to this therapy is emerging, placing further emphasis on the need to make a mycological diagnosis using molecular based methods. Outbreaks in SOT recipients, particularly renal transplants, are increasingly described, and likely caused by human-to-human spread, highlighting the need for efficient infection control policies and sensitive diagnostic assays. Widespread prophylaxis is the best measure to gain control of outbreak situations. This review will summarize diagnostic options, cover prophylactic and therapeutic management in the main at risk populations, while also covering aspects of managing resistant disease, outbreak situations, and paediatric PcP. Full article
(This article belongs to the Special Issue Treatments for Fungal Infections)
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6 pages, 366 KiB  
Article
A Ketoconazole Susceptibility Test for Malassezia pachydermatis Using Modified Leeming–Notman Agar
by Bo-Young Hsieh, Wei-Hsun Chao, Yi-Jing Xue and Jyh-Mirn Lai
J. Fungi 2018, 4(4), 126; https://doi.org/10.3390/jof4040126 - 16 Nov 2018
Cited by 2 | Viewed by 4280
Abstract
The aim of this study was to establish a ketoconazole susceptibility test for Malassezia pachydermatis using modified Leeming–Notman agar (mLNA). The susceptibilities of 33 M. pachydermatis isolates obtained by modified CLSI M27-A3 method were compared with the results by disk diffusion method, which [...] Read more.
The aim of this study was to establish a ketoconazole susceptibility test for Malassezia pachydermatis using modified Leeming–Notman agar (mLNA). The susceptibilities of 33 M. pachydermatis isolates obtained by modified CLSI M27-A3 method were compared with the results by disk diffusion method, which used different concentrations of ketoconazole on 6 mm diameter paper disks. Results showed that 93.9% (31/33) of the minimum inhibitory concentration (MIC) values obtained from both methods were similar (consistent with two methods within 2 dilutions). M. pachydermatis BCRC 21676 and Candida parapsilosis ATCC 22019 were used to verify the results obtained from the disk diffusion and modified CLSI M27-A3 tests, and they were found to be consistent. Therefore, the current study concludes that this new novel test—using different concentrations of reagents on cartridge disks to detect MIC values against ketoconazole—can be a cost-effective, time-efficient, and less technically demanding alternative to existing methods. Full article
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12 pages, 14782 KiB  
Review
An Invertebrate Host to Study Fungal Infections, Mycotoxins and Antifungal Drugs: Tenebrio molitor
by Patrícia Canteri de Souza, Carla Custódio Caloni, Duncan Wilson and Ricardo Sergio Almeida
J. Fungi 2018, 4(4), 125; https://doi.org/10.3390/jof4040125 - 12 Nov 2018
Cited by 27 | Viewed by 7781
Abstract
Faced with ethical conflict and social pressure, researchers have increasingly chosen to use alternative models over vertebrates in their research. Since the innate immune system is evolutionarily conserved in insects, the use of these animals in research is gaining ground. This review discusses [...] Read more.
Faced with ethical conflict and social pressure, researchers have increasingly chosen to use alternative models over vertebrates in their research. Since the innate immune system is evolutionarily conserved in insects, the use of these animals in research is gaining ground. This review discusses Tenebrio molitor as a potential model host for the study of pathogenic fungi. Larvae of T. molitor are known as cereal pests and, in addition, are widely used as animal and human feed. A number of studies on mechanisms of the humoral system, especially in the synthesis of antimicrobial peptides, which have similar characteristics to vertebrates, have been performed. These studies demonstrate the potential of T. molitor larvae as a model host that can be used to study fungal virulence, mycotoxin effects, host immune responses to fungal infection, and the action of antifungal compounds. Full article
(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)
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12 pages, 1892 KiB  
Article
Development of an Improved Carotenoid Extraction Method to Characterize the Carotenoid Composition under Oxidative Stress and Cold Temperature in the Rock Inhabiting Fungus Knufia petricola A95
by Kerstin Flieger, Nicole Knabe and Jörg Toepel
J. Fungi 2018, 4(4), 124; https://doi.org/10.3390/jof4040124 - 09 Nov 2018
Cited by 14 | Viewed by 4714
Abstract
Black yeasts are a highly specified group of fungi, which are characterized by a high resistance against stress factors. There are several factors enabling the cells to survive harsh environmental conditions. One aspect is the pigmentation, the melanin black yeasts often display a [...] Read more.
Black yeasts are a highly specified group of fungi, which are characterized by a high resistance against stress factors. There are several factors enabling the cells to survive harsh environmental conditions. One aspect is the pigmentation, the melanin black yeasts often display a highly diverse carotenoid spectrum. Determination and characterization of carotenoids depend on an efficient extraction and separation, especially for black yeast, which is characterized by thick cell walls. Therefore, specific protocols are needed to ensure reliable analyses regarding stress responses in these fungi. Here we present both. First, we present a method to extract and analyze carotenoids and secondly we present the unusual carotenoid composition of the black yeast Knufia petricola A95. Mechanical treatment combined with an acetonitrile extraction gave us very good extraction rates with a high reproducibility. The presented extraction and elution protocol separates the main carotenoids (7) in K. petricola A95 and can be extended for the detection of additional carotenoids in other species. K. petricola A95 displays an unusual carotenoid composition, with mainly didehydrolycopene, torulene, and lycopene. The pigment composition varied in dependency to oxidative stress but remained relatively constant if the cells were cultivated under low temperature. Future experiments have to be carried out to determine if didehydrolycopene functions as a protective agent itself or if it serves as a precursor for antioxidative pigments like torulene and torularhodin, which could be produced after induction under stress conditions. Black yeasts are a promising source for carotenoid production and other substances. To unravel the potential of these fungi, new methods and studies are needed. The established protocol allows the determination of carotenoid composition in black yeasts. Full article
(This article belongs to the Special Issue Fungal Polyketides and Other Secondary Metabolites)
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16 pages, 1265 KiB  
Review
Caenorhabditis elegans as a Model Host to Monitor the Candida Infection Processes
by Asmaa B. Elkabti, Luca Issi and Reeta P. Rao
J. Fungi 2018, 4(4), 123; https://doi.org/10.3390/jof4040123 - 07 Nov 2018
Cited by 30 | Viewed by 6041
Abstract
C. elegans has several advantages as an experimental host for the study of infectious diseases. Worms are easily maintained and propagated on bacterial lawns. The worms can be frozen for long term storage and still maintain viability years later. Their short generation time [...] Read more.
C. elegans has several advantages as an experimental host for the study of infectious diseases. Worms are easily maintained and propagated on bacterial lawns. The worms can be frozen for long term storage and still maintain viability years later. Their short generation time and large brood size of thousands of worms grown on a single petri dish, makes it relatively easy to maintain at a low cost. The typical wild type adult worm grows to approximately 1.5 mm in length and are transparent, allowing for the identification of several internal organs using an affordable dissecting microscope. A large collection of loss of function mutant strains are readily available from the C. elegans genetic stock center, making targeted genetic studies in the nematode possible. Here we describe ways in which this facile model host has been used to study Candida albicans, an opportunistic fungal pathogen that poses a serious public health threat. Full article
(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)
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15 pages, 737 KiB  
Review
Candida Interactions with the Oral Bacterial Microbiota
by Daniel Montelongo-Jauregui and Jose L. Lopez-Ribot
J. Fungi 2018, 4(4), 122; https://doi.org/10.3390/jof4040122 - 03 Nov 2018
Cited by 45 | Viewed by 6777
Abstract
The human oral cavity is normally colonized by a wide range of microorganisms, including bacteria, fungi, Archaea, viruses, and protozoa. Within the different oral microenvironments these organisms are often found as part of highly organized microbial communities termed biofilms, which display consortial behavior. [...] Read more.
The human oral cavity is normally colonized by a wide range of microorganisms, including bacteria, fungi, Archaea, viruses, and protozoa. Within the different oral microenvironments these organisms are often found as part of highly organized microbial communities termed biofilms, which display consortial behavior. Formation and maintenance of these biofilms are highly dependent on the direct interactions between the different members of the microbiota, as well as on the released factors that influence the surrounding microbial populations. These complex biofilm dynamics influence oral health and disease. In the latest years there has been an increased recognition of the important role that interkingdom interactions, in particular those between fungi and bacteria, play within the oral cavity. Candida spp., and in particular C. albicans, are among the most important fungi colonizing the oral cavity of humans and have been found to participate in these complex microbial oral biofilms. C. albicans has been reported to interact with individual members of the oral bacterial microbiota, leading to either synergistic or antagonistic relationships. In this review we describe some of the better characterized interactions between Candida spp. and oral bacteria. Full article
(This article belongs to the Special Issue Oral Mycobiome)
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17 pages, 372 KiB  
Review
An Update on the Roles of Non-albicans Candida Species in Vulvovaginitis
by Olufunmilola Makanjuola, Felix Bongomin and Samuel A. Fayemiwo
J. Fungi 2018, 4(4), 121; https://doi.org/10.3390/jof4040121 - 31 Oct 2018
Cited by 99 | Viewed by 9138
Abstract
Candida species are one of the commonest causes of vaginitis in healthy women of reproductive age. Vulvovaginal candidiasis (VVC) is characterized by vulvovaginal itching, redness and discharge. Candida albicans, which is a common genito-urinary tract commensal, has been the prominent species and [...] Read more.
Candida species are one of the commonest causes of vaginitis in healthy women of reproductive age. Vulvovaginal candidiasis (VVC) is characterized by vulvovaginal itching, redness and discharge. Candida albicans, which is a common genito-urinary tract commensal, has been the prominent species and remains the most common fungal agent isolated from clinical samples of patients diagnosed with VVC. In recent times, however, there has been a notable shift in the etiology of candidiasis with non-albicans Candida (NAC) species gaining prominence. The NAC species now account for approximately 10% to as high as 45% of VVC cases in some studies. This is associated with treatment challenges and a slightly different clinical picture. NAC species vaginitis is milder in presentation, often occur in patients with underlying chronic medical conditions and symptoms tend to be more recurrent or chronic compared with C. albicans vaginitis. C. glabrata is the most common cause of NAC-VVC. C. tropicalis, C. krusei, C. parapsilosis, and C. guilliermondii are the other commonly implicated species. Treatment failure is common in NAC-VVC, since some of these species are intrinsically resistant or show low susceptibilities to commonly used antifungal agents. This article reviews the etiology, pathogenesis, clinical features, diagnosis, and management of NAC vulvovaginitis. Full article
16 pages, 257 KiB  
Review
Therapy of Non-Dermatophytic Mycoses in Animals
by Daniel Elad
J. Fungi 2018, 4(4), 120; https://doi.org/10.3390/jof4040120 - 30 Oct 2018
Cited by 9 | Viewed by 4755
Abstract
This review focuses on aspects of antimycotic therapy specific to veterinary medicine. In the first part, drug availability, limited mostly by economic consideration but also by clinical applicability and specific adverse effects, is described for polyenes, 5 fluorocytosine, azoles, echinocandins and terbinafine. In [...] Read more.
This review focuses on aspects of antimycotic therapy specific to veterinary medicine. In the first part, drug availability, limited mostly by economic consideration but also by clinical applicability and specific adverse effects, is described for polyenes, 5 fluorocytosine, azoles, echinocandins and terbinafine. In the second part, current knowledge and experience in the treatment of selected fungal infections are overviewed. These mycoses include disseminated mold infections in small animals (dogs and cats) and avian species, upper respiratory tract infections of small animals (sino-nasal and sino-orbital aspergillosis) and horses (guttural pouch mycosis), eumycetoma, infections caused by dimorphic fungi, (blastomycosis, histoplasmosis, coccidioidomycosis, paracoccidioidomycosis and sporothrichosis) and by yeasts and yeast-like microorganism (Cryptococcus spp. and Malassezia pachydermatis). Full article
(This article belongs to the Special Issue Treatments for Fungal Infections)
28 pages, 4731 KiB  
Review
Adhesins of Yeasts: Protein Structure and Interactions
by Ronnie G. Willaert
J. Fungi 2018, 4(4), 119; https://doi.org/10.3390/jof4040119 - 27 Oct 2018
Cited by 54 | Viewed by 7853
Abstract
The ability of yeast cells to adhere to other cells or substrates is crucial for many yeasts. The budding yeast Saccharomyces cerevisiae can switch from a unicellular lifestyle to a multicellular one. A crucial step in multicellular lifestyle adaptation is self-recognition, self-interaction, and [...] Read more.
The ability of yeast cells to adhere to other cells or substrates is crucial for many yeasts. The budding yeast Saccharomyces cerevisiae can switch from a unicellular lifestyle to a multicellular one. A crucial step in multicellular lifestyle adaptation is self-recognition, self-interaction, and adhesion to abiotic surfaces. Infectious yeast diseases such as candidiasis are initiated by the adhesion of the yeast cells to host cells. Adhesion is accomplished by adhesin proteins that are attached to the cell wall and stick out to interact with other cells or substrates. Protein structures give detailed insights into the molecular mechanism of adhesin-ligand interaction. Currently, only the structures of a very limited number of N-terminal adhesion domains of adhesins have been solved. Therefore, this review focuses on these adhesin protein families. The protein architectures, protein structures, and ligand interactions of the flocculation protein family of S. cerevisiae; the epithelial adhesion family of C. glabrata; and the agglutinin-like sequence protein family of C. albicans are reviewed and discussed. Full article
(This article belongs to the Special Issue Cell Adhesion in Fungal Life and Pathogenesis)
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19 pages, 1004 KiB  
Review
Applications of Invertebrate Animal Models to Dimorphic Fungal Infections
by Junya L. Singulani, Liliana Scorzoni, Haroldo C. De Oliveira, Caroline M. Marcos, Patricia A. Assato, Ana Marisa Fusco-Almeida and Maria José S. Mendes-Giannini
J. Fungi 2018, 4(4), 118; https://doi.org/10.3390/jof4040118 - 19 Oct 2018
Cited by 23 | Viewed by 5799
Abstract
Dimorphic fungi can be found in the yeast form during infection and as hyphae in the environment and are responsible for a large number of infections worldwide. Invertebrate animals have been shown to be convenient models in the study of fungal infections. These [...] Read more.
Dimorphic fungi can be found in the yeast form during infection and as hyphae in the environment and are responsible for a large number of infections worldwide. Invertebrate animals have been shown to be convenient models in the study of fungal infections. These models have the advantages of being low cost, have no ethical issues, and an ease of experimentation, time-efficiency, and the possibility of using a large number of animals per experiment compared to mammalian models. Invertebrate animal models such as Galleria mellonella, Caenorhabditis elegans, and Acanthamoeba castellanii have been used to study dimorphic fungal infections in the context of virulence, innate immune response, and the efficacy and toxicity of antifungal agents. In this review, we first summarize the features of these models. In this aspect, the growth temperature, genome sequence, availability of different strains, and body characteristics should be considered in the model choice. Finally, we discuss the contribution and advances of these models, with respect to dimorphic fungi Paracoccidioides spp., Histoplasma capsulatum, Blastomyces dermatitidis, Sporothrix spp., and Talaromyces marneffei (Penicillium marneffei). Full article
(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)
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13 pages, 1292 KiB  
Review
Nebulised N-Acetylcysteine for Unresponsive Bronchial Obstruction in Allergic Brochopulmonary Aspergillosis: A Case Series and Review of the Literature
by Akaninyene Otu, Philip Langridge and David W. Denning
J. Fungi 2018, 4(4), 117; https://doi.org/10.3390/jof4040117 - 15 Oct 2018
Cited by 10 | Viewed by 5502
Abstract
Many chronic lung diseases are characterized by the hypersecretion of mucus. In these conditions, the administration of mucoactive agents is often indicated as adjuvant therapy. N-acetylcysteine (NAC) is a typical example of a mucolytic agent. A retrospective review of patients with pulmonary [...] Read more.
Many chronic lung diseases are characterized by the hypersecretion of mucus. In these conditions, the administration of mucoactive agents is often indicated as adjuvant therapy. N-acetylcysteine (NAC) is a typical example of a mucolytic agent. A retrospective review of patients with pulmonary aspergillosis treated at the National Aspergillosis Centre in Manchester, United Kingdom, with NAC between November 2015 and November 2017 was carried out. Six Caucasians with Aspergillus lung disease received NAC to facilitate clearance of their viscid bronchial mucus secretions. One patient developed immediate bronchospasm on the first dose and could not be treated. Of the remainder, two (33%) derived benefit, with increased expectoration and reduced symptoms. Continued response was sustained over 6–7 months, without any apparent toxicity. In addition, a systematic review of the literature is provided to analyze the utility of NAC in the management of respiratory conditions which have unresponsive bronchial obstruction as a feature. Full article
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4 pages, 215 KiB  
Editorial
Special Issue “Sporothrix and Sporotrichosis”
by Héctor M. Mora-Montes
J. Fungi 2018, 4(4), 116; https://doi.org/10.3390/jof4040116 - 12 Oct 2018
Cited by 6 | Viewed by 3585
Abstract
Sporotrichosis is a neglected, deep-seated fungal infection traditionally associated with Sporothrix
schenckii, a dimorphic organism that was first described more than a century ago in human and
rat specimens [1].[...] Full article
(This article belongs to the Special Issue Sporothrix and Sporotrichosis)
23 pages, 382 KiB  
Review
Advances in the Treatment of Mycoses in Pediatric Patients
by Elias Iosifidis, Savvas Papachristou and Emmanuel Roilides
J. Fungi 2018, 4(4), 115; https://doi.org/10.3390/jof4040115 - 11 Oct 2018
Cited by 16 | Viewed by 5730
Abstract
The main indications for antifungal drug administration in pediatrics are reviewed as well as an update of the data of antifungal agents and antifungal policies performed. Specifically, antifungal therapy in three main areas is updated as follows: (a) Prophylaxis of premature neonates against [...] Read more.
The main indications for antifungal drug administration in pediatrics are reviewed as well as an update of the data of antifungal agents and antifungal policies performed. Specifically, antifungal therapy in three main areas is updated as follows: (a) Prophylaxis of premature neonates against invasive candidiasis; (b) management of candidemia and meningoencephalitis in neonates; and (c) prophylaxis, empiric therapy, and targeted antifungal therapy in children with primary or secondary immunodeficiencies. Fluconazole remains the most frequent antifungal prophylactic agent given to high-risk neonates and children. However, the emergence of fluconazole resistance, particularly in non-albicans Candida species, should be considered during preventive or empiric therapy. In very-low birth-weight neonates, although fluconazole is used as antifungal prophylaxis in neonatal intensive care units (NICU’s) with relatively high incidence of invasive candidiasis (IC), its role is under continuous debate. Amphotericin B, primarily in its liposomal formulation, remains the mainstay of therapy for treating neonatal and pediatric yeast and mold infections. Voriconazole is indicated for mold infections except for mucormycosis in children >2 years. Newer triazoles-such as posaconazole and isavuconazole-as well as echinocandins, are either licensed or under study for first-line or salvage therapy, whereas combination therapy is kept for refractory cases. Full article
(This article belongs to the Special Issue Treatments for Fungal Infections)
4 pages, 182 KiB  
Case Report
Beta-Glucanemia after Coronary Artery Bypass Graft Surgery: A Case Report
by Ashley Styczynski, Hector Bonilla, Elizabeth Treynor, Jolly Shashank, Yonglong Zhang and Malcolm Finkelman
J. Fungi 2018, 4(4), 114; https://doi.org/10.3390/jof4040114 - 02 Oct 2018
Cited by 2 | Viewed by 2803
Abstract
Blood salvage techniques are increasingly being used during surgical procedures to reduce the need for exogenous blood products. The blood recovered from the surgical field through aspiration or absorption by surgical sponges is reinfused into a patient. A 65-year old patient who underwent [...] Read more.
Blood salvage techniques are increasingly being used during surgical procedures to reduce the need for exogenous blood products. The blood recovered from the surgical field through aspiration or absorption by surgical sponges is reinfused into a patient. A 65-year old patient who underwent coronary artery bypass grafting using blood salvage techniques developed a fever on post-op day 3 and was noted to have an elevated β-d-glucan level, a marker of systemic fungal infections. Ultimately, no fungal infection was identified, β-d-glucan levels slowly decreased and the patient demonstrated clinical improvement. To determine whether blood salvage procedures led to his elevated β-d-glucan levels, the surgical sponges were tested for elutable levels of β-d-glucan. The β-d-glucan content of the eluents was measured using the Fungitell® IVD kit (Associates of Cape Cod, Inc.; East Falmouth, MA). The β-d-glucan levels were found to be in concentrations 10,000-times greater than the limit of detection for human serum. While various studies have demonstrated both the immunomodulatory and pro-inflammatory effects of β-d-glucan, the physiologic impact of such high levels of β-d-glucan post-operatively remains unknown. Additionally, the persistence of detectable β-d-glucan up to several weeks after surgical procedures presents a challenge for the diagnosis of invasive fungal infections. Further studies are needed to assess the beta-glucanemia-related safety of surgical materials and their potential biological effects. Full article
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