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J. Fungi, Volume 6, Issue 1 (March 2020) – 24 articles

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Open AccessArticle
Cysteine Dioxygenase Enzyme Activity and Gene Expression in the Dimorphic Pathogenic Fungus Histoplasma capsulatum Is in both the Mold and Yeast Morphotypes and Exhibits Substantial Strain Variation
J. Fungi 2020, 6(1), 24; https://doi.org/10.3390/jof6010024 - 13 Feb 2020
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Abstract
In the dimorphism (mold/yeast) Histoplasma capsulatum (Hc) literature are reports that yeast (the so-called pathogenic form) uniquely expresses a cysteine dioxygenase (CDO, approx. 10,500 dal) activity which the mold morphotype (the so-called saprophytic soil form) does not express (C.F., Kumar et [...] Read more.
In the dimorphism (mold/yeast) Histoplasma capsulatum (Hc) literature are reports that yeast (the so-called pathogenic form) uniquely expresses a cysteine dioxygenase (CDO, approx. 10,500 dal) activity which the mold morphotype (the so-called saprophytic soil form) does not express (C.F., Kumar et al., Biochem 22, 762, 1983). This yeast-specific CDO activity is postulated to play a critical role in the mold-to-yeast shift. A number of years ago, our lab isolated the gene encoding the Hc cysteine dioxygenase (CDO1, Genbank accession AY804144) and noted significant expression in the mold morphotype of several Histoplasma strains and also determined that the predicted protein would be over double the 10,500 dal reported by Kumar et al. Our report demonstrates (in the class 1 Downs strain, the class 2 G271B strain and two Panamanian strains, 184AS and 186AS) that the CDO1 gene is expressed in both the mold and yeast morphotypes and both morphotypes show significant CDO activity. Furthermore, we show via a FLAG-tag analysis that the expressed protein is approximately 24.7 ± 2.4 kd, in agreement with the putative protein sequence (determined from cDNA sequence) which yields 23.8 kd and is consistent with most other eukaryotic CDO enzymes. Additionally, we demonstrate that intracellular cysteine levels are actually significantly higher in the mold form of the two Panamanian strains, 184AS and 186AS, equal in both mold and yeast in the class 1 Downs strain and significantly higher in yeast of the more pathogenic class 2 G217B strain. Full article
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Open AccessReview
An Overview on Conventional and Non-Conventional Therapeutic Approaches for the Treatment of Candidiasis and Underlying Resistance Mechanisms in Clinical Strains
J. Fungi 2020, 6(1), 23; https://doi.org/10.3390/jof6010023 - 10 Feb 2020
Viewed by 154
Abstract
Fungal infections and, in particular, those caused by species of the Candida genus, are growing at an alarming rate and have high associated rates of mortality and morbidity. These infections, generally referred as candidiasis, range from common superficial rushes caused by an overgrowth [...] Read more.
Fungal infections and, in particular, those caused by species of the Candida genus, are growing at an alarming rate and have high associated rates of mortality and morbidity. These infections, generally referred as candidiasis, range from common superficial rushes caused by an overgrowth of the yeasts in mucosal surfaces to life-threatening disseminated mycoses. The success of currently used antifungal drugs to treat candidiasis is being endangered by the continuous emergence of resistant strains, specially among non-albicans Candida species. In this review article, the mechanisms of action of currently used antifungals, with emphasis on the mechanisms of resistance reported in clinical isolates, are reviewed. Novel approaches being taken to successfully inhibit growth of pathogenic Candida species, in particular those based on the exploration of natural or synthetic chemicals or on the activity of live probiotics, are also reviewed. It is expected that these novel approaches, either used alone or in combination with traditional antifungals, may contribute to foster the identification of novel anti-Candida therapies. Full article
(This article belongs to the Special Issue Molecular Diagnostics of Fungal Infections)
Open AccessReview
Monoclonal Antibodies as Tools to Combat Fungal Infections
J. Fungi 2020, 6(1), 22; https://doi.org/10.3390/jof6010022 - 04 Feb 2020
Viewed by 209
Abstract
Antibodies represent an important element in the adaptive immune response and a major tool to eliminate microbial pathogens. For many bacterial and viral infections, efficient vaccines exist, but not for fungal pathogens. For a long time, antibodies have been assumed to be of [...] Read more.
Antibodies represent an important element in the adaptive immune response and a major tool to eliminate microbial pathogens. For many bacterial and viral infections, efficient vaccines exist, but not for fungal pathogens. For a long time, antibodies have been assumed to be of minor importance for a successful clearance of fungal infections; however this perception has been challenged by a large number of studies over the last three decades. In this review, we focus on the potential therapeutic and prophylactic use of monoclonal antibodies. Since systemic mycoses normally occur in severely immunocompromised patients, a passive immunization using monoclonal antibodies is a promising approach to directly attack the fungal pathogen and/or to activate and strengthen the residual antifungal immune response in these patients. Full article
(This article belongs to the Special Issue Fungal Vaccines and Immunotherapeutics)
Open AccessReview
Contributions of the Biofilm Matrix to Candida Pathogenesis
J. Fungi 2020, 6(1), 21; https://doi.org/10.3390/jof6010021 - 03 Feb 2020
Viewed by 260
Abstract
In healthcare settings, Candida spp. cause invasive disease with high mortality. The overwhelming majority of cases are associated with the use of critically-needed medical devices, such as vascular catheters. On the surface of these indwelling materials, Candida forms resilient, adherent biofilm communities. A [...] Read more.
In healthcare settings, Candida spp. cause invasive disease with high mortality. The overwhelming majority of cases are associated with the use of critically-needed medical devices, such as vascular catheters. On the surface of these indwelling materials, Candida forms resilient, adherent biofilm communities. A hallmark characteristic of this process is the production of an extracellular matrix, which promotes fungal adhesion and provides protection from external threats. In this review, we highlight the medical relevance of device-associated Candida biofilms and draw attention to the process of Candida-biofilm-matrix production. We provide an update on the current understanding of how biofilm extracellular matrix contributes to pathogenicity, particularly through its roles in the promoting antifungal drug tolerance and immune evasion. Full article
(This article belongs to the Special Issue Pathogenesis of Candidiasis)
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Open AccessArticle
Breakthrough Bloodstream Infections Caused by Echinocandin-Resistant Candida tropicalis: An Emerging Threat to Immunocompromised Patients with Hematological Malignancies
J. Fungi 2020, 6(1), 20; https://doi.org/10.3390/jof6010020 - 31 Jan 2020
Viewed by 377
Abstract
Background. Candida tropicalis is a virulent fungal pathogen for which echinocandins are the primary therapy. Emergence of resistance to echinocandins of C. tropicalis carries potentially ominous therapeutic implications. Methods. We describe herein two patients with breakthrough C. tropicalis fungemia during echinocandin therapy, characterize [...] Read more.
Background. Candida tropicalis is a virulent fungal pathogen for which echinocandins are the primary therapy. Emergence of resistance to echinocandins of C. tropicalis carries potentially ominous therapeutic implications. Methods. We describe herein two patients with breakthrough C. tropicalis fungemia during echinocandin therapy, characterize their molecular mechanism of resistance, and systematically review 13 previously reported cases of echinocandin-resistant C. tropicalis bloodstream infections (BSIs) and other diseases. Results. Among these 15 patients with echinocandin-resistant C. tropicalis infections, the median age was 61 years (ages 28–84 years) and 13 (86%) were immunocompromised. Thirteen (86%) of all patients had a history of pervious or concurrent exposure to echinocandins. Isolates of C. tropicalis from 11 cases, including the two index cases, underwent DNA sequencing of the FKS1 gene for mutations known to confer echinocandin resistance. The amino acid substitution Ser654Pro was shown in four cases, while other FKS1 mutations encoded Ser80S/Pro, Phe641Leu, Phe641Ser, Ser80S/Pro substitutions. These mutational events were not associated with collateral increases in minimum inhibitory concentrations to antifungal triazoles and amphotericin B. Overall mortality in patients with echinocandin-resistant C. tropicalis infections was 40%. Among those six patients who died, two received monotherapy with voriconazole, one was treated with fluconazole, one remained on caspofungin, and two were switched to liposomal amphotericin B. Nine patients (60%) survived after being treated with an antifungal agent other than an echinocandin. Conclusions. Emergence of resistance to echinocandins by C. tropicalis, occurs during antifungal therapy, is associated with high mortality, is mediated by a diverse range of FKS1 mutations, retains in vitro susceptibility to triazoles and amphotericin B, and constitutes an emerging threat to patients with hematological malignancies. Full article
Open AccessReview
The Squeaky Yeast Gets Greased: The Roles of Host Lipids in the Clearance of Pathogenic Fungi
J. Fungi 2020, 6(1), 19; https://doi.org/10.3390/jof6010019 - 31 Jan 2020
Viewed by 251
Abstract
Fungal infections remain a global health threat with high morbidity and mortality. The human immune system must, therefore, perpetually defend against invasive fungal infections. Phagocytosis is critical for the clearance of fungal pathogens, as this cellular process allows select immune cells to internalize [...] Read more.
Fungal infections remain a global health threat with high morbidity and mortality. The human immune system must, therefore, perpetually defend against invasive fungal infections. Phagocytosis is critical for the clearance of fungal pathogens, as this cellular process allows select immune cells to internalize and destroy invading fungal cells. While much is known about the protein players that enable phagocytosis, the various roles that lipids play during this fundamental innate immune process are still being illuminated. In this review, we describe recent discoveries that shed new light on the mechanisms by which host lipids enable the phagocytic uptake and clearance of fungal pathogens. Full article
(This article belongs to the Special Issue Lipids and Fungal Infectious Diseases)
Open AccessReview
Blood Aspergillus PCR: The Good, the Bad, and the Ugly
J. Fungi 2020, 6(1), 18; https://doi.org/10.3390/jof6010018 - 27 Jan 2020
Viewed by 479
Abstract
Invasive Aspergillosis (IA) is one of the most common invasive fungal diseases and is accompanied by high morbidity and mortality. In order to maximize patient outcomes and survival, early and rapid diagnosis has been shown to be pivotal. Hence, diagnostic tools aiding and [...] Read more.
Invasive Aspergillosis (IA) is one of the most common invasive fungal diseases and is accompanied by high morbidity and mortality. In order to maximize patient outcomes and survival, early and rapid diagnosis has been shown to be pivotal. Hence, diagnostic tools aiding and improving the diagnostic process are ambitiously searched for. In this context, polymerase chain reaction (PCR) may represent a potential candidate. Its additional value and benefits in diagnosis have been demonstrated and are scientifically established. Nevertheless, standardized and widespread usage is sparse because several factors influence diagnostic quality and need to be considered in order to optimize diagnostic performance and outcome. In the following review, the current role of PCR in the diagnosis of IA is explored, with special focus on the strengths and limitations of PCR in different settings. Full article
(This article belongs to the Special Issue Molecular Diagnostics of Fungal Infections)
Open AccessEditorial
Acknowledgement to Reviewers of Journal of Fungi in 2019
J. Fungi 2020, 6(1), 17; https://doi.org/10.3390/jof6010017 - 21 Jan 2020
Viewed by 188
Abstract
The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...] Full article
Open AccessReview
On Commensalism of Candida
J. Fungi 2020, 6(1), 16; https://doi.org/10.3390/jof6010016 - 17 Jan 2020
Viewed by 344
Abstract
Candida species are both opportunistic fungal pathogens and common members of the human mycobiome. Over the years, the main focus of the fungal field has been on understanding the pathogenic potential and disease manifestation of these organisms. Therefore, understanding of their commensal lifestyle, [...] Read more.
Candida species are both opportunistic fungal pathogens and common members of the human mycobiome. Over the years, the main focus of the fungal field has been on understanding the pathogenic potential and disease manifestation of these organisms. Therefore, understanding of their commensal lifestyle, interactions with host epithelial barriers, and initial transition into pathogenesis is less developed. In this review, we will describe the current knowledge on the commensal lifestyle of these fungi, how they are able to adhere to and colonize host epithelial surfaces, compete with other members of the microbiota, and interact with the host immune response, as well as their transition into opportunistic pathogens by invading the gastrointestinal epithelium. Full article
(This article belongs to the Special Issue Pathogenesis of Candidiasis)
Open AccessReview
Oral Candidiasis: A Disease of Opportunity
J. Fungi 2020, 6(1), 15; https://doi.org/10.3390/jof6010015 - 16 Jan 2020
Viewed by 472
Abstract
Oral candidiasis, commonly referred to as “thrush,” is an opportunistic fungal infection that commonly affects the oral mucosa. The main causative agent, Candida albicans, is a highly versatile commensal organism that is well adapted to its human host; however, changes in the [...] Read more.
Oral candidiasis, commonly referred to as “thrush,” is an opportunistic fungal infection that commonly affects the oral mucosa. The main causative agent, Candida albicans, is a highly versatile commensal organism that is well adapted to its human host; however, changes in the host microenvironment can promote the transition from one of commensalism to pathogen. This transition is heavily reliant on an impressive repertoire of virulence factors, most notably cell surface adhesins, proteolytic enzymes, morphologic switching, and the development of drug resistance. In the oral cavity, the co-adhesion of C. albicans with bacteria is crucial for its persistence, and a wide range of synergistic interactions with various oral species were described to enhance colonization in the host. As a frequent colonizer of the oral mucosa, the host immune response in the oral cavity is oriented toward a more tolerogenic state and, therefore, local innate immune defenses play a central role in maintaining Candida in its commensal state. Specifically, in addition to preventing Candida adherence to epithelial cells, saliva is enriched with anti-candidal peptides, considered to be part of the host innate immunity. The T helper 17 (Th17)-type adaptive immune response is mainly involved in mucosal host defenses, controlling initial growth of Candida and inhibiting subsequent tissue invasion. Animal models, most notably the mouse model of oropharyngeal candidiasis and the rat model of denture stomatitis, are instrumental in our understanding of Candida virulence factors and the factors leading to host susceptibility to infections. Given the continuing rise in development of resistance to the limited number of traditional antifungal agents, novel therapeutic strategies are directed toward identifying bioactive compounds that target pathogenic mechanisms to prevent C. albicans transition from harmless commensal to pathogen. Full article
(This article belongs to the Special Issue Pathogenesis of Candidiasis)
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Open AccessReview
Unraveling How Candida albicans Forms Sexual Biofilms
J. Fungi 2020, 6(1), 14; https://doi.org/10.3390/jof6010014 - 15 Jan 2020
Viewed by 624
Abstract
Biofilms, structured and densely packed communities of microbial cells attached to surfaces, are considered to be the natural growth state for a vast majority of microorganisms. The ability to form biofilms is an important virulence factor for most pathogens, including the opportunistic human [...] Read more.
Biofilms, structured and densely packed communities of microbial cells attached to surfaces, are considered to be the natural growth state for a vast majority of microorganisms. The ability to form biofilms is an important virulence factor for most pathogens, including the opportunistic human fungal pathogen Candida albicans. C. albicans is one of the most prevalent fungal species of the human microbiota that asymptomatically colonizes healthy individuals. However, C. albicans can also cause severe and life-threatening infections when host conditions permit (e.g., through alterations in the host immune system, pH, and resident microbiota). Like many other pathogens, this ability to cause infections depends, in part, on the ability to form biofilms. Once formed, C. albicans biofilms are often resistant to antifungal agents and the host immune response, and can act as reservoirs to maintain persistent infections as well as to seed new infections in a host. The majority of C. albicans clinical isolates are heterozygous (a/α) at the mating type-like (MTL) locus, which defines Candida mating types, and are capable of forming robust biofilms when cultured in vitro. These “conventional” biofilms, formed by MTL-heterozygous (a/α) cells, have been the primary focus of C. albicans biofilm research to date. Recent work in the field, however, has uncovered novel mechanisms through which biofilms are generated by C. albicans cells that are homozygous or hemizygous (a/a, a/Δ, α/α, or α/Δ) at the MTL locus. In these studies, the addition of pheromones of the opposite mating type can induce the formation of specialized “sexual” biofilms, either through the addition of synthetic peptide pheromones to the culture, or in response to co-culturing of cells of the opposite mating types. Although sexual biofilms are generally less robust than conventional biofilms, they could serve as a protective niche to support genetic exchange between mating-competent cells, and thus may represent an adaptive mechanism to increase population diversity in dynamic environments. Although conventional and sexual biofilms appear functionally distinct, both types of biofilms are structurally similar, containing yeast, pseudohyphal, and hyphal cells surrounded by an extracellular matrix. Despite their structural similarities, conventional and sexual biofilms appear to be governed by distinct transcriptional networks and signaling pathways, suggesting that they may be adapted for, and responsive to, distinct environmental conditions. Here we review sexual biofilms and compare and contrast them to conventional biofilms of C. albicans. Full article
(This article belongs to the Special Issue Fungal Biofilms 2020)
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Open AccessReview
A Re-Evaluation of the Relationship between Morphology and Pathogenicity in Candida Species
J. Fungi 2020, 6(1), 13; https://doi.org/10.3390/jof6010013 - 13 Jan 2020
Viewed by 370
Abstract
Many pathogenic Candida species possess the ability to undergo a reversible morphological transition from yeast to filamentous cells. In Candida albicans, the most frequently isolated human fungal pathogen, multiple lines of evidence strongly suggest that this transition is associated with virulence and [...] Read more.
Many pathogenic Candida species possess the ability to undergo a reversible morphological transition from yeast to filamentous cells. In Candida albicans, the most frequently isolated human fungal pathogen, multiple lines of evidence strongly suggest that this transition is associated with virulence and pathogenicity. While it has generally been assumed that non-albicans Candida species (NACS) are less pathogenic than C. albicans, in part, because they do not filament as well, definitive evidence is lacking. Interestingly, however, a recent study suggests that filamentation of NACS is associated with reduced, rather than increased, pathogenicity. These findings, in turn, challenge conventional views and suggest that there are fundamental evolutionary differences in the morphology–pathogenicity relationship in C. albicans vs. NACS. The findings also raise many new and intriguing questions and open new avenues for future research, which are discussed. Full article
(This article belongs to the Special Issue Pathogenesis of Candidiasis)
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Open AccessReview
Detecting Azole-Antifungal Resistance in Aspergillus fumigatus by Pyrosequencing
J. Fungi 2020, 6(1), 12; https://doi.org/10.3390/jof6010012 - 10 Jan 2020
Viewed by 583
Abstract
Guidelines on the diagnosis and management of Aspergillus disease recommend a multi-test approach including CT scans, culture, fungal biomarker tests, microscopy and fungal PCR. The first-line treatment of confirmed invasive aspergillosis (IA) consists of drugs in the azole family; however, the emergence of [...] Read more.
Guidelines on the diagnosis and management of Aspergillus disease recommend a multi-test approach including CT scans, culture, fungal biomarker tests, microscopy and fungal PCR. The first-line treatment of confirmed invasive aspergillosis (IA) consists of drugs in the azole family; however, the emergence of azole-resistant isolates has negatively impacted the management of IA. Failure to detect azole-resistance dramatically increases the mortality rates of azole-treated patients. Despite drug susceptibility tests not being routinely performed currently, we suggest including resistance testing whilst diagnosing Aspergillus disease. Multiple tools, including DNA sequencing, are available to screen for drug-resistant Aspergillus in clinical samples. This is particularly beneficial as a large proportion of IA samples are culture negative, consequently impeding susceptibility testing through conventional methods. Pyrosequencing is a promising in-house DNA sequencing method that can rapidly screen for genetic hotspots associated with antifungal resistance. Pyrosequencing outperforms other susceptibility testing methods due to its fast turnaround time, accurate detection of polymorphisms within critical genes, including simultaneous detection of wild type and mutated sequences, and—most importantly—it is not limited to specific genes nor fungal species. Here we review current diagnostic methods and highlight the potential of pyrosequencing to aid in a diagnosis complete with a resistance profile to improve clinical outcomes. Full article
(This article belongs to the Special Issue Molecular Diagnostics of Fungal Infections)
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Open AccessBrief Report
Molecular Detection of Aspergillus: Application of a Real-Time PCR Multiplex Assay in Tissue Samples
J. Fungi 2020, 6(1), 11; https://doi.org/10.3390/jof6010011 - 10 Jan 2020
Viewed by 257
Abstract
Diagnosis of invasive fungal infections is complex, and the lack of standardization of molecular methods is still a challenge. Several methods are available for the diagnosis of invasive aspergillosis, but their effectiveness will depend on the studied population, the patients’ comorbidities, and the [...] Read more.
Diagnosis of invasive fungal infections is complex, and the lack of standardization of molecular methods is still a challenge. Several methods are available for the diagnosis of invasive aspergillosis, but their effectiveness will depend on the studied population, the patients’ comorbidities, and the use of mold active prophylaxis, among others. The ability to determine the identity of the infecting Aspergillus species, and to detect mutations conferring specific resistance patterns directly from DNA extracted from the biological product, is an advantage of nucleic acid testing compared with antigen-based assays. In this study, we present laboratory cases where the diagnosis of aspergillosis was performed using a real-time multiplex PCR for the detection of Aspergillus DNA in tissue samples, showing its usefulness as one more tool in the diagnosis of aspergillosis in tissue samples. Aspergillus real-time multiplex PCR was also used to detect azole-resistance in some cases. In the majority of the PCR positive cases, cultures remained negative after 60 days. The PCR assay directed to Aspergillus gave positive signals for Aspergillus fumigatus sensu stricto. Results were confirmed by panfungal PCR, followed by sequencing, revealing 100% homology with Aspergillus fumigatus sensu stricto. Mutations conferring azole resistance were not detected. Full article
(This article belongs to the Special Issue Molecular Diagnostics of Fungal Infections)
Open AccessReview
The Impact of Gene Dosage and Heterozygosity on the Diploid Pathobiont Candida albicans
J. Fungi 2020, 6(1), 10; https://doi.org/10.3390/jof6010010 - 27 Dec 2019
Viewed by 477
Abstract
Candida albicans is a fungal species that can colonize multiple niches in the human host where it can grow either as a commensal or as an opportunistic pathogen. The genome of C. albicans has long been of considerable interest, given that it is [...] Read more.
Candida albicans is a fungal species that can colonize multiple niches in the human host where it can grow either as a commensal or as an opportunistic pathogen. The genome of C. albicans has long been of considerable interest, given that it is highly plastic and can undergo a wide variety of alterations. These changes play a fundamental role in determining C. albicans traits and have been shown to enable adaptation both to the host and to antifungal drugs. C. albicans isolates contain a heterozygous diploid genome that displays variation from the level of single nucleotides to largescale rearrangements and aneuploidy. The heterozygous nature of the genome is now increasingly recognized as being central to C. albicans biology, as the relative fitness of isolates has been shown to correlate with higher levels of overall heterozygosity. Moreover, loss of heterozygosity (LOH) events can arise frequently, either at single polymorphisms or at a chromosomal level, and both can alter the behavior of C. albicans cells during infection or can modulate drug resistance. In this review, we examine genome plasticity in this pathobiont focusing on how gene dosage variation and loss of heterozygosity events can arise and how these modulate C. albicans behavior. Full article
(This article belongs to the Special Issue Pathogenesis of Candidiasis)
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Open AccessArticle
Quantification of Pneumocystis jirovecii: Cross-Platform Comparison of One qPCR Assay with Leading Platforms and Six Master Mixes
J. Fungi 2020, 6(1), 9; https://doi.org/10.3390/jof6010009 - 26 Dec 2019
Viewed by 475
Abstract
Diagnosis of Pneumocystis jirovecii pneumonia relies on nucleic acid quantification in respiratory samples. Lack of standardization among molecular assays results in significant differences among assays/centers. To further promote standardization, we compared four thermocyclers and six master mixes for the detection of P. jirovecii [...] Read more.
Diagnosis of Pneumocystis jirovecii pneumonia relies on nucleic acid quantification in respiratory samples. Lack of standardization among molecular assays results in significant differences among assays/centers. To further promote standardization, we compared four thermocyclers and six master mixes for the detection of P. jirovecii. Whole nucleic acid (WNA) was extracted from broncho-alveolar lavages. Positive and negative sample extracts were pooled to get enough homogeneous materials. Three master mixes were tested to detect DNA by qPCR (D1, D2, and D3), and three to detect WNA by reverse transcriptase qPCR (W1, W2, and W3) manufactured by Roche, Eurogentec, Applied Biosystem, Invitrogen and Thermofischer Scientific. Experiments were performed on four thermocyclers (Roche LightCycler 480, Qiagen Rotor-Gene Q, Applied Biosystem ABI7500, and QuantStudio). Comparison of quantitative cycle (Cq) values between the methods targeting WNA versus DNA showed lower Cq values for WNA, independently of thermocycler and master mix. For high and low fungal loads, ∆Cq values between DNA and WNA amplification were 6.97 (±2.95) and 5.81 (±3.30), respectively (p < 0.0001). Regarding DNA detection, lower Cqs were obtained with D1 compared to D2 and D3, with median ∆Cq values of 2.6 (p = 0.015) and 2.9 (p = 0.039) respectively. Regarding WNA detection, no mix was superior to the others. PCR efficiency was not significantly different according to the qPCR platform (p = 0.14). This study confirmed the superiority of WNA over DNA detection. A calibration method (e.g., an international standard) for accurate comparative assessment of fungal load seems necessary. Full article
(This article belongs to the Special Issue Molecular Diagnostics of Fungal Infections)
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Open AccessReview
N-Acetylglucosamine Regulates Morphogenesis and Virulence Pathways in Fungi
J. Fungi 2020, 6(1), 8; https://doi.org/10.3390/jof6010008 - 24 Dec 2019
Viewed by 526
Abstract
N-acetylglucosamine (GlcNAc) is being increasingly recognized for its ability to stimulate cell signaling. This amino sugar is best known as a component of cell wall peptidoglycan in bacteria, cell wall chitin in fungi and parasites, exoskeletons of arthropods, and the extracellular matrix [...] Read more.
N-acetylglucosamine (GlcNAc) is being increasingly recognized for its ability to stimulate cell signaling. This amino sugar is best known as a component of cell wall peptidoglycan in bacteria, cell wall chitin in fungi and parasites, exoskeletons of arthropods, and the extracellular matrix of animal cells. In addition to these structural roles, GlcNAc is now known to stimulate morphological and stress responses in a wide range of organisms. In fungi, the model organisms Saccharomyces cerevisiae and Schizosaccharomyces pombe lack the ability to respond to GlcNAc or catabolize it, so studies with the human pathogen Candida albicans have been providing new insights into the ability of GlcNAc to stimulate cellular responses. GlcNAc potently induces C. albicans to transition from budding to filamentous hyphal growth. It also promotes an epigenetic switch from White to Opaque cells, which differ in morphology, metabolism, and virulence properties. These studies have led to new discoveries, such as the identification of the first eukaryotic GlcNAc transporter. Other results have shown that GlcNAc can induce signaling in C. albicans in two ways. One is to act as a signaling molecule independent of its catabolism, and the other is that its catabolism can cause the alkalinization of the extracellular environment, which provides an additional stimulus to form hyphae. GlcNAc also induces the expression of virulence genes in the C. albicans, indicating it can influence pathogenesis. Therefore, this review will describe the recent advances in understanding the role of GlcNAc signaling pathways in regulating C. albicans morphogenesis and virulence. Full article
(This article belongs to the Special Issue Pathogenesis of Candidiasis)
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Open AccessArticle
Chromosome-Level Comprehensive Genome of Mangrove Sediment-Derived Fungus Penicillium variabile HXQ-H-1
J. Fungi 2020, 6(1), 7; https://doi.org/10.3390/jof6010007 - 23 Dec 2019
Viewed by 376
Abstract
Penicillium is an ascomycetous genus widely distributed in the natural environment and is one of the dominant fungi involved in the decomposition of mangroves, which can produce a variety of antitumor compounds and bioactive substances. However, in mangrove ecosystems there is no complete [...] Read more.
Penicillium is an ascomycetous genus widely distributed in the natural environment and is one of the dominant fungi involved in the decomposition of mangroves, which can produce a variety of antitumor compounds and bioactive substances. However, in mangrove ecosystems there is no complete genome in this genus. In this study, we isolated a fungus strain named Penicillium variabile HXQ-H-1 from coast mangrove (Fujian Province, China). We generated a chromosome-level genome with total size of 33.32 Mb, scaffold N50 of 5.23 Mb and contig N50 of 96.74 kb. Additionally, we anchored about 95.91% assembly sequences into the longest seven scaffolds, and predicted 10,622 protein-coding genes, in which 99.66% could be annotated by eight protein databases. The secondary metabolites analysis reveals the strain has various gene clusters involving polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS) and terpene synthase that may have a largely capacity of biotechnological potential. Comparison genome analysis between Penicillium variabile and Talaromyces islandicus reveals a small difference in the total number of genes, whereas HXQ-H-1 has a higher gene number with COG functional annotation. Evolutionary relationship of Penicillum based on genome-wide data was carried out for the first time, showing the strain HXQ-H-1 is closely related to Talaromyces islandicus. This genomic resource may provide a new resource for development of novel bioactive antibiotics, drug candidates and precursors in Penicillium variabile. Full article
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Open AccessEditorial
Special Issue: Mucorales and Mucormycosis
J. Fungi 2020, 6(1), 6; https://doi.org/10.3390/jof6010006 - 23 Dec 2019
Viewed by 371
Abstract
Mucormycosis is a life-threatening infection, occurring mainly in immunocompromised patients, but also in immunocompetent patients after traumatic injuries [...] Full article
(This article belongs to the Special Issue Mucorales and Mucormycosis)
Open AccessReview
Candida spp./Bacteria Mixed Biofilms
J. Fungi 2020, 6(1), 5; https://doi.org/10.3390/jof6010005 - 20 Dec 2019
Viewed by 459
Abstract
The ability to form biofilms is a common feature of microorganisms, such as bacteria or fungi. These consortiums can colonize a variety of surfaces, such as host tissues, dentures, and catheters, resulting in infections highly resistant to drugs, when compared with their planktonic [...] Read more.
The ability to form biofilms is a common feature of microorganisms, such as bacteria or fungi. These consortiums can colonize a variety of surfaces, such as host tissues, dentures, and catheters, resulting in infections highly resistant to drugs, when compared with their planktonic counterparts. This refractory effect is particularly critical in polymicrobial biofilms involving both fungi and bacteria. This review emphasizes Candida spp.-bacteria biofilms, the epidemiology of this community, the challenges in the eradication of such biofilms, and the most relevant treatments. Full article
(This article belongs to the Special Issue Pathogenesis of Candidiasis)
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Open AccessReview
Biotic Environments Supporting the Persistence of Clinically Relevant Mucormycetes
J. Fungi 2020, 6(1), 4; https://doi.org/10.3390/jof6010004 - 20 Dec 2019
Cited by 1 | Viewed by 366
Abstract
Clinically relevant members of the Mucorales group can grow and are found in diverse ecological spaces such as soil, dust, water, decomposing vegetation, on and in food, and in hospital environments but are poorly represented in mycobiome studies of outdoor and indoor air. [...] Read more.
Clinically relevant members of the Mucorales group can grow and are found in diverse ecological spaces such as soil, dust, water, decomposing vegetation, on and in food, and in hospital environments but are poorly represented in mycobiome studies of outdoor and indoor air. Occasionally, Mucorales are found in water-damaged buildings. This mini review examines a number of specialised biotic environments, including those revealed by natural disasters and theatres of war, that support the growth and persistence of these fungi. However, we are no further forward in understanding exposure pathways or the chronicity of exposure that results in the spectrum of clinical presentations of mucormycosis. Full article
(This article belongs to the Special Issue Mucorales and Mucormycosis)
Open AccessEditorial
Histoplasmosis in Persons Living with HIV
J. Fungi 2020, 6(1), 3; https://doi.org/10.3390/jof6010003 - 18 Dec 2019
Viewed by 308
Abstract
The increase in the number of immunocompromised persons, following the HIV pandemic, has led to a dramatic amplification of the number of patients with progressive disseminated histoplasmosis [...] Full article
(This article belongs to the Special Issue Histoplasma and Histoplasmosis)
Open AccessEditorial
Candida auris—“Ten Years After”
J. Fungi 2020, 6(1), 2; https://doi.org/10.3390/jof6010002 - 18 Dec 2019
Viewed by 406
Abstract
We would like to thank all contributors to this Special Issue on Candida auris [...] Full article
(This article belongs to the Special Issue Candida auris)
Open AccessReview
The Role of Molecular Tests in the Diagnosis of Disseminated Histoplasmosis
J. Fungi 2020, 6(1), 1; https://doi.org/10.3390/jof6010001 - 18 Dec 2019
Viewed by 341
Abstract
Histoplasmosis is an emerging fungal disease, with global distribution. The disseminated form of the disease is a more severe infection, generally associated with AIDS. Classic diagnostic methods for histoplasmosis consist of microscopy, culture, and histopathology. More recently, the importance of Histoplasma antigen detection [...] Read more.
Histoplasmosis is an emerging fungal disease, with global distribution. The disseminated form of the disease is a more severe infection, generally associated with AIDS. Classic diagnostic methods for histoplasmosis consist of microscopy, culture, and histopathology. More recently, the importance of Histoplasma antigen detection has dominated the literature on histoplasmosis diagnosis, but the relevance of molecular assays has not been as much studied. Here we describe the results of a systematic literature review focusing on studies that mainly compared immunological techniques (Histoplasma urine antigen detection) with molecular tests for the diagnosis of histoplasmosis. In addition to the review of comparative studies using such diagnostic techniques, the literature on polymerase chain reaction (PCR) tests in patients with disseminated histoplasmosis is also summarized. Two studies reported the comparison between immunological and molecular methods applied simultaneously for the diagnosis of disseminated histoplasmosis. PCR demonstrates a satisfactory performance assisting in the detection of Histoplasma spp. DNA in clinical samples. Full article
(This article belongs to the Special Issue Molecular Diagnostics of Fungal Infections)
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