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J. Fungi, Volume 5, Issue 1 (March 2019)

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Cover Story (view full-size image) Candida albicans yeast cells can be induced to form hyphae by many well-studied environmental [...] Read more.
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Open AccessReview Global Epidemiology of Mucormycosis
J. Fungi 2019, 5(1), 26; https://doi.org/10.3390/jof5010026
Received: 11 February 2019 / Revised: 14 March 2019 / Accepted: 16 March 2019 / Published: 21 March 2019
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Abstract
Mucormycosis is an angio-invasive fungal infection, associated with high morbidity and mortality. A change in the epidemiology of mucormycosis has been observed in recent years with the rise in incidence, new causative agents and susceptible population. The rise has been perceived globally, but [...] Read more.
Mucormycosis is an angio-invasive fungal infection, associated with high morbidity and mortality. A change in the epidemiology of mucormycosis has been observed in recent years with the rise in incidence, new causative agents and susceptible population. The rise has been perceived globally, but it is very high in the Asian continent. Though diabetes mellitus overshadow all other risk factors in Asia, post-tuberculosis and chronic renal failure have emerged as new risk groups. The rhino-cerebral form of mucormycosis is most commonly seen in patients with diabetes mellitus, whereas, pulmonary mucormycosis in patients with haematological malignancy and transplant recipients. In immunocompetent hosts, cutaneous mucormycosis is commonly seen following trauma. The intriguing clinical entity, isolated renal mucormycosis in immunocompetent patients is only reported from China and India. A new clinical entity, indolent mucormycosis in nasal sinuses, is recently recognized. The causative agents of mucormycosis vary across different geographic locations. Though Rhizopus arrhizus is the most common agent isolated worldwide, Apophysomyces variabilis is predominant in Asia and Lichtheimia species in Europe. The new causative agents, Rhizopus homothallicus, Mucor irregularis, and Thamnostylum lucknowense are reported from Asia. In conclusion, with the change in epidemiology of mucormycosis country-wise studies are warranted to estimate disease burden in different risk groups, analyse the clinical disease pattern and identify the new etiological agents. Full article
(This article belongs to the Special Issue Mucorales and Mucormycosis)
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Open AccessReview Mucormycosis in Burn Patients
J. Fungi 2019, 5(1), 25; https://doi.org/10.3390/jof5010025
Received: 7 February 2019 / Revised: 19 March 2019 / Accepted: 20 March 2019 / Published: 21 March 2019
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Abstract
Patients with extensive burns are an important group at risk for cutaneous mucormycosis. This study aimed to perform a systematic review of all reported mucormycosis cases in burn patients from 1990 onward. A Medline search yielded identification of 7 case series, 3 outbreaks, [...] Read more.
Patients with extensive burns are an important group at risk for cutaneous mucormycosis. This study aimed to perform a systematic review of all reported mucormycosis cases in burn patients from 1990 onward. A Medline search yielded identification of 7 case series, 3 outbreaks, and 25 individual cases reports. The prevalence reached 0.04%–0.6%. The median age was 42–48 in the case series and outbreaks, except for the studies from military centers (23.5–32.5) and in individual reports (29.5). The median total body surface area reached 42.5%–65%. Various skin lesions were described, none being pathognomonic: the diagnosis was mainly reached because of extensive necrotic lesions sometimes associated with sepsis. Most patients were treated with systemic amphotericin B or liposomal amphotericin B, and all underwent debridement and/or amputation. Mortality reached 33%–100% in the case series, 29%–62% during outbreaks, and 40% in individual cases. Most patients were diagnosed using histopathology and/or culture. Mucorales qPCR showed detection of circulating DNA 2–24 days before the standard diagnosis. Species included the main clinically relevant mucorales (i.e., Mucor, Rhizopus, Absidia/Lichtheimia, Rhizomucor) but also more uncommon mucorales such as Saksenaea or Apophysomyces. Contact with soil was reported in most individual cases. Bandages were identified as the source of contamination in two nosocomial outbreaks. Full article
(This article belongs to the Special Issue Mucorales and Mucormycosis)
Open AccessReview Molecular Strategies to Diagnose Mucormycosis
J. Fungi 2019, 5(1), 24; https://doi.org/10.3390/jof5010024
Received: 2 February 2019 / Revised: 14 March 2019 / Accepted: 18 March 2019 / Published: 20 March 2019
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Abstract
Molecular techniques have provided a new understanding of the epidemiology of mucormycosis and improved the diagnosis and therapeutic management of this life-threatening disease. PCR amplification and sequencing were first applied to better identify isolates that were grown from cultures of biopsies or bronchalveolar [...] Read more.
Molecular techniques have provided a new understanding of the epidemiology of mucormycosis and improved the diagnosis and therapeutic management of this life-threatening disease. PCR amplification and sequencing were first applied to better identify isolates that were grown from cultures of biopsies or bronchalveolar lavage samples that were collected in patients with Mucorales infection. Subsequently, molecular techniques were used to identify the fungus directly from the infected tissues or from bronchalveolar lavage, and they helped to accurately identify Mucorales fungi in tissue samples when the cultures were negative. However, these tools require invasive sampling (biospsy, bronchalveolar lavage), which is not feasible in patients in poor condition in Hematology or Intensive Care units. Very recently, PCR-based procedures to detect Mucorales DNA in non-invasive samples, such as plasma or serum, have proved successful in diagnosing mucormycosis early in all patients, whatever the clinical status, and these procedures are becoming essential to improving patient outcome. Full article
(This article belongs to the Special Issue Mucorales and Mucormycosis)
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Open AccessReview Disease Entities in Mucormycosis
J. Fungi 2019, 5(1), 23; https://doi.org/10.3390/jof5010023
Received: 29 January 2019 / Revised: 9 March 2019 / Accepted: 11 March 2019 / Published: 14 March 2019
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Abstract
Mucormycosis is an emerging life-threatening fungal infection caused by Mucorales. This infection occurs mainly in immunocompromised patients, especially with hematological malignancy, transplantation, or diabetes mellitus. Rhino-orbito-cerebral and pulmonary mucormycosis are the predominant forms. Interestingly, location is associated with the underlying disease as [...] Read more.
Mucormycosis is an emerging life-threatening fungal infection caused by Mucorales. This infection occurs mainly in immunocompromised patients, especially with hematological malignancy, transplantation, or diabetes mellitus. Rhino-orbito-cerebral and pulmonary mucormycosis are the predominant forms. Interestingly, location is associated with the underlying disease as pulmonary mucormycosis is more frequent in hematological malignancy patients whereas rhino-orbito-cerebral mucormycosis is associated with diabetes. Cutaneous mucormycosis results from direct inoculation, mainly after trauma or surgery. Gastro-intestinal mucormycosis occurs after ingestion of contaminated food or with contaminated device and involves the stomach or colon. Disseminated disease is the most severe form and is associated with profound immunosuppression. Uncommon presentations with endocarditis, osteoarticluar or isolated cerebral infections are also described. Finally, health-care associated mucormycosis is a matter of concern in premature newborns and burn units. Clinical symptoms and CT scan findings are not specific, only the early reversed halo sign is associated with pulmonary mucormycosis. Circulating Mucorales DNA detection is a recent promising diagnostic tool that may lead to improving the diagnosis and prompting therapeutic initiation that should include antifungal treatment, correction of the underlying disease and surgery when feasible. Full article
(This article belongs to the Special Issue Mucorales and Mucormycosis)
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Open AccessArticle Candida albicans Morphology-Dependent Host FGF-2 Response as a Potential Therapeutic Target
J. Fungi 2019, 5(1), 22; https://doi.org/10.3390/jof5010022
Received: 10 January 2019 / Revised: 20 February 2019 / Accepted: 1 March 2019 / Published: 5 March 2019
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Abstract
Angiogenesis mediated by proteins such as Fibroblast Growth Factor-2 (FGF-2) is a vital component of normal physiological processes and has also been implicated in contributing to the disease state associated with various microbial infections. Previous studies by our group and others have shown [...] Read more.
Angiogenesis mediated by proteins such as Fibroblast Growth Factor-2 (FGF-2) is a vital component of normal physiological processes and has also been implicated in contributing to the disease state associated with various microbial infections. Previous studies by our group and others have shown that Candida albicans, a common agent of candidiasis, induces FGF-2 secretion in vitro and angiogenesis in brains and kidneys during systemic infections. However, the underlying mechanism(s) via which the fungus increases FGF-2 production and the role(s) that FGF-2/angiogenesis plays in C. albicans disease remain unknown. Here we show, for the first time, that C. albicans hyphae (and not yeast cells) increase the FGF-2 response in human endothelial cells. Moreover, Candidalysin, a toxin secreted exclusively by C. albicans in the hyphal state, is required to induce this response. Our in vivo studies show that in the systemic C. albicans infection model, mice treated with FGF-2 exhibit significantly higher mortality rates when compared to untreated mice not given the angiogenic growth factor. Even treatment with fluconazole could not fully rescue infected animals that were administered FGF-2. Our data suggest that the increase of FGF-2 production/angiogenesis induced by Candidalysin contributes to the pathogenicity of C. albicans. Full article
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Open AccessReview Regulation of Candida albicans Hyphal Morphogenesis by Endogenous Signals
J. Fungi 2019, 5(1), 21; https://doi.org/10.3390/jof5010021
Received: 10 January 2019 / Revised: 25 February 2019 / Accepted: 26 February 2019 / Published: 28 February 2019
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Abstract
Candida albicans is a human commensal fungus that is able to assume several morphologies, including yeast, hyphal, and pseudohyphal. Under a range of conditions, C. albicans performs a regulated switch to the filamentous morphology, characterized by the emergence of a germ tube from [...] Read more.
Candida albicans is a human commensal fungus that is able to assume several morphologies, including yeast, hyphal, and pseudohyphal. Under a range of conditions, C. albicans performs a regulated switch to the filamentous morphology, characterized by the emergence of a germ tube from the yeast cell, followed by a mold-like growth of branching hyphae. This transition from yeast to hyphal growth has attracted particular attention, as it has been linked to the virulence of C. albicans as an opportunistic human pathogen. Signal transduction pathways that mediate the induction of the hyphal transcription program upon the imposition of external stimuli have been extensively investigated. However, the hyphal morphogenesis transcription program can also be induced by internal cellular signals, such as inhibition of cell cycle progression, and conversely, the inhibition of hyphal extension can repress hyphal-specific gene expression, suggesting that endogenous cellular signals are able to modulate hyphal gene expression as well. Here we review recent developments in the regulation of the hyphal morphogenesis of C. albicans, with emphasis on endogenous morphogenetic signals. Full article
(This article belongs to the Special Issue Regulation of Fungal Morphogenesis and Gene Expression)
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Open AccessReview Recent Findings in Onychomycosis and Their Application for Appropriate Treatment
J. Fungi 2019, 5(1), 20; https://doi.org/10.3390/jof5010020
Received: 17 January 2019 / Revised: 15 February 2019 / Accepted: 19 February 2019 / Published: 22 February 2019
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Abstract
Onychomycosis is mainly caused by two dermatophyte species, Trichophyton rubrum and Trichophyton interdigitale. A study of nail invasion mechanisms revealed that the secreted subtilisin Sub6, which has never been detected under in vitro growth conditions, was the main protease secreted by T. [...] Read more.
Onychomycosis is mainly caused by two dermatophyte species, Trichophyton rubrum and Trichophyton interdigitale. A study of nail invasion mechanisms revealed that the secreted subtilisin Sub6, which has never been detected under in vitro growth conditions, was the main protease secreted by T. rubrum and T. interdigitale during infection. In contrast, most of the proteases secreted during the digestion of keratin in vitro were not detected in infected nails. The hypothesis that proteases isolated from dermatophytes grown in a keratin medium are virulence factors is no longer supported. Non-dermatophyte fungi can also be infectious agents in nails. It is necessary to identify the infectious fungus in onychomycosis to prescribe adequate treatment, as moulds such as Fusarium spp. and Aspergillus spp. are insensitive to standard treatments with terbinafine or itraconazole, which are usually applied for dermatophytes. In these refractory cases, topical amphotericin B treatment has shown to be effective. Terbinafine treatment failure against dermatophytes is also possible, and is usually due to resistance caused by a missense mutation in the squalene epoxidase enzyme targeted by the drug. Trichophyton resistance to terbinafine treatment is an emerging problem, and a switch to azole-based treatment may be necessary to cure such cases of onychomycosis. Full article
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Open AccessArticle Changing Epidemiology of Invasive Candidiasis in Children during a 10-Year Period
J. Fungi 2019, 5(1), 19; https://doi.org/10.3390/jof5010019
Received: 29 December 2018 / Revised: 15 February 2019 / Accepted: 21 February 2019 / Published: 22 February 2019
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Abstract
Candida species are a common cause of invasive infection in neonates and children. The aim of our study was to evaluate the epidemiology and microbiology of invasive candidiasis (IC) in the largest tertiary Greek pediatric hospital during a 10-year period. A retrospective cohort [...] Read more.
Candida species are a common cause of invasive infection in neonates and children. The aim of our study was to evaluate the epidemiology and microbiology of invasive candidiasis (IC) in the largest tertiary Greek pediatric hospital during a 10-year period. A retrospective cohort study was performed from January 2008 to December 2017. Identification of species and antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) methodology. During the study period, 178 cases of IC were recorded. The tissue distribution included blood (87.1%), cerebrospinal (7.9%), peritoneal (3.9%) and pleural fluids (1.1%). Candida albicans and Candida parapsilosis (sensu lato) were the most frequently isolated species (47.8% and 28.7% respectively). From period 2008–2012 to period 2013–2017, a significant decrease in IC rates was detected (0.21 cases/1000 hospitalization days VS 0.11 cases/1000 hospitalization days, P = 0.040), while median minimum inhibitory concentrations (MICs) of amphotericin B were significantly increased for both C. albicans and C. parapsilosis (sl) (P = 0.037 and P = 0.004 respectively). The decrease in IC rates may reflect the increased awareness as well as the effective infection control initiatives and antifungal interventions. However, the significant increase in the MICs for amphotericin B and echinocandins such as caspofungin, raises concerns about their common use as first-line treatment. Epidemiologic monitoring is, therefore, critically important in order to evaluate and optimize therapeutic protocols for IC in pediatric populations. Full article
(This article belongs to the Special Issue Fungal Epidemiology)
Open AccessArticle Chronic Pulmonary Aspergillosis in Patients with Underlying Respiratory Disorders in Cuba—A Pilot Study
J. Fungi 2019, 5(1), 18; https://doi.org/10.3390/jof5010018
Received: 13 December 2018 / Revised: 14 February 2019 / Accepted: 15 February 2019 / Published: 22 February 2019
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Abstract
Chronic pulmonary aspergillosis (CPA) is a fungal infection with high mortality and morbidity rates. This disease is caused by several Aspergillus species and affects patients with an underlying respiratory condition. This pilot study aims to recognize CPA among patients with different respiratory diseases. [...] Read more.
Chronic pulmonary aspergillosis (CPA) is a fungal infection with high mortality and morbidity rates. This disease is caused by several Aspergillus species and affects patients with an underlying respiratory condition. This pilot study aims to recognize CPA among patients with different respiratory diseases. Twenty-one out of 47 patients were classified as CPA based on the examination of clinical signs and symptoms, radiological findings, mycological culture of respiratory samples and analysis of Aspergillus IgG antibodies. There was a close association between high levels of Aspergillus IgG antibodies and the presence of cavities. Although Aspergillus flavus was the predominant species among clinical isolates, the number of isolates was small to reach conclusions on the prevalence of this species as main cause of CPA in Cuba. From the eleven evaluable patients for the treatment with itraconazole (Lozartil®), nine improved their health status while two did not show any recovery. This drug is included in the therapy schemes for aspergillosis in Cuba. Full article
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Open AccessReview Linking Cellular Morphogenesis with Antifungal Treatment and Susceptibility in Candida Pathogens
J. Fungi 2019, 5(1), 17; https://doi.org/10.3390/jof5010017
Received: 7 January 2019 / Revised: 11 February 2019 / Accepted: 13 February 2019 / Published: 21 February 2019
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Abstract
Fungal infections are a growing public health concern, and an increasingly important cause of human mortality, with Candida species being amongst the most frequently encountered of these opportunistic fungal pathogens. Several Candida species are polymorphic, and able to transition between distinct morphological states, [...] Read more.
Fungal infections are a growing public health concern, and an increasingly important cause of human mortality, with Candida species being amongst the most frequently encountered of these opportunistic fungal pathogens. Several Candida species are polymorphic, and able to transition between distinct morphological states, including yeast, hyphal, and pseudohyphal forms. While not all Candida pathogens are polymorphic, the ability to undergo morphogenesis is linked with the virulence of many of these pathogens. There are also many connections between Candida morphogenesis and antifungal drug treatment and susceptibility. Here, we review how Candida morphogenesis—a key virulence trait—is linked with antifungal drugs and antifungal drug resistance. We highlight how antifungal therapeutics are able to modulate morphogenesis in both sensitive and drug-resistant Candida strains, the shared signaling pathways that mediate both morphogenesis and the cellular response to antifungal drugs and drug resistance, and the connection between Candida morphology, drug resistance, and biofilm growth. We further review the development of anti-virulence drugs, and targeting Candida morphogenesis as a novel therapeutic strategy to target fungal pathogens. Together, this review highlights important connections between fungal morphogenesis, virulence, and susceptibility to antifungals. Full article
(This article belongs to the Special Issue Regulation of Fungal Morphogenesis and Gene Expression)
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Open AccessArticle Effect of Marine Basidiomycetes Fulvifomes sp.-Derived Ergosterol Peroxide on Cytotoxicity and Apoptosis Induction in MCF-7 Cell Line
J. Fungi 2019, 5(1), 16; https://doi.org/10.3390/jof5010016
Received: 15 December 2018 / Revised: 8 February 2019 / Accepted: 11 February 2019 / Published: 13 February 2019
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Abstract
The aim of the present study is to extract the bioactive compounds which can induce the apoptosis in breast cancer cell line MCF-7 by marine basidiomycetes. Internal Transcribed Spacer (ITS) sequences based molecular taxonomic study confirmed that collected the marine basidiomycetes belongs to [...] Read more.
The aim of the present study is to extract the bioactive compounds which can induce the apoptosis in breast cancer cell line MCF-7 by marine basidiomycetes. Internal Transcribed Spacer (ITS) sequences based molecular taxonomic study confirmed that collected the marine basidiomycetes belongs to Fulvifomes sp. Further, the isolated compounds from the Fulvifomes sp. confirmed as ergosterol peroxide (EP) by spectroscopic studies. The compound inhibited 50% of the cell growth (IC50) at the concentration of 40 µg/mL and induced 90% cell death (IC 90) at the concentration of 80 µg/mL. The ergosterol peroxide generated Reactive Oxygen Species (ROS) and induced apoptotic cell death in MCF-7. Ethidium bromide/Acridine Orange (Et/Br) staining showed the increased number of early and late apoptosis in treated MCF-7 cells. The compounds treated cells indicated the significant loss of mitochondrial membrane potential (Δψm) with p < 0.05. The induction of apoptosis by marine basidiomycetes derived ergosterol peroxide was confirmed by chromatin condensation in MCF7 cells using Hoechst staining 33342. Full article
(This article belongs to the Special Issue Fungal Polyketides and Other Secondary Metabolites)
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Open AccessArticle High-Throughput Sequencing to Investigate Phytopathogenic Fungal Propagules Caught in Baited Insect Traps
J. Fungi 2019, 5(1), 15; https://doi.org/10.3390/jof5010015
Received: 14 January 2019 / Revised: 2 February 2019 / Accepted: 4 February 2019 / Published: 12 February 2019
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Abstract
Studying the means of dispersal of plant pathogens is crucial to better understand the dynamic interactions involved in plant infections. On one hand, entomologists rely mostly on both traditional molecular methods and morphological characteristics, to identify pests. On the other hand, high-throughput sequencing [...] Read more.
Studying the means of dispersal of plant pathogens is crucial to better understand the dynamic interactions involved in plant infections. On one hand, entomologists rely mostly on both traditional molecular methods and morphological characteristics, to identify pests. On the other hand, high-throughput sequencing (HTS) is becoming the go-to avenue for scientists studying phytopathogens. These organisms sometimes infect plants, together with insects. Considering the growing number of exotic insect introductions in Canada, forest pest-management efforts would benefit from the development of a high-throughput strategy to investigate the phytopathogenic fungal and oomycete species interacting with wood-boring insects. We recycled formerly discarded preservative fluids from the Canadian Food Inspection Agency annual survey using insect traps and analysed more than one hundred samples originating from across Canada. Using the Ion Torrent Personal Genome Machine (PGM) HTS technology and fusion primers, we performed metabarcoding to screen unwanted fungi and oomycetes species, including Phytophthora spp. Community profiling was conducted on the four different wood-boring, insect-attracting semiochemicals; although the preservative (contained ethanol) also attracted other insects. Phytopathogenic fungi (e.g., Leptographium spp. and Meria laricis in the pine sawyer semiochemical) and oomycetes (mainly Peronospora spp. and Pythium aff. hypogynum in the General Longhorn semiochemical), solely associated with one of the four types of semiochemicals, were detected. This project demonstrated that the insect traps’ semiochemical microbiome represents a new and powerful matrix for screening phytopathogens. Compared to traditional diagnostic techniques, the fluids allowed for a faster and higher throughput assessment of the biodiversity contained within. Additionally, minimal modifications to this approach would allow it to be used in other phytopathology fields. Full article
(This article belongs to the Special Issue Fungal-Insect Interactions)
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Open AccessReview Invasive Aspergillosis in Pediatric Leukemia Patients: Prevention and Treatment
J. Fungi 2019, 5(1), 14; https://doi.org/10.3390/jof5010014
Received: 4 December 2018 / Revised: 5 February 2019 / Accepted: 5 February 2019 / Published: 11 February 2019
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Abstract
The purpose of this article is to review and update the strategies for prevention and treatment of invasive aspergillosis (IA) in pediatric patients with leukemia and in patients with hematopoietic stem cell transplantation. The major risk factors associated with IA will be described [...] Read more.
The purpose of this article is to review and update the strategies for prevention and treatment of invasive aspergillosis (IA) in pediatric patients with leukemia and in patients with hematopoietic stem cell transplantation. The major risk factors associated with IA will be described since their recognition constitutes the first step of prevention. The latter is further analyzed into chemoprophylaxis and non-pharmacologic approaches. Triazoles are the mainstay of anti-fungal prophylaxis while the other measures revolve around reducing exposure to mold spores. Three levels of treatment have been identified: (a) empiric, (b) pre-emptive, and (c) targeted treatment. Empiric is initiated in febrile neutropenic patients and uses mainly caspofungin and liposomal amphotericin B (LAMB). Pre-emptive is a diagnostic driven approach attempting to reduce unnecessary use of anti-fungals. Treatment targeted at proven or probable IA is age-dependent, with voriconazole and LAMB being the cornerstones in >2yrs and <2yrs age groups, respectively. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts) Printed Edition available
Open AccessArticle In Vitro Anti-Biofilm Activities of Citral and Thymol Against Candida Tropicalis
J. Fungi 2019, 5(1), 13; https://doi.org/10.3390/jof5010013
Received: 31 December 2018 / Revised: 25 January 2019 / Accepted: 31 January 2019 / Published: 3 February 2019
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Abstract
Candida tropicalis is an emerging non-albicans Candida species which is pathogenic to the immune-compromised humans, especially in tropical countries, including India. The acquired resistance of Candida species towards antifungal therapies is of major concern. Moreover, limited efficacy and dosage constraint of synthetic [...] Read more.
Candida tropicalis is an emerging non-albicans Candida species which is pathogenic to the immune-compromised humans, especially in tropical countries, including India. The acquired resistance of Candida species towards antifungal therapies is of major concern. Moreover, limited efficacy and dosage constraint of synthetic drugs have indicated the prerequisite of finding new and natural drugs for treatment. In the present study, we have compared the influence of citral and thymol on C. tropicalis and its biofilm along with expression levels of certain antifungal tolerance genes. The antifungal and anti-biofilm activities of the both were studied using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt (XTT) reduction assay, field emission scanning electron microscope (FE-SEM) and confocal laser scanning microscope (CLSM) and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis. Citral and thymol have damaged the cells with distorted surface and less viability. Quantitative real-time PCR analysis showed augmented expression of the cell membrane biosynthesis genes including ERG11/CYT450 against citral and the cell wall related tolerance genes involving CNB1 against thymol thus, depicting their differential mode of actions. Full article
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Open AccessEditorial Current Status and Trends in Alternative Models to Study Fungal Pathogens
J. Fungi 2019, 5(1), 12; https://doi.org/10.3390/jof5010012
Received: 18 January 2019 / Accepted: 22 January 2019 / Published: 26 January 2019
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Abstract
Fungal infections affect over a billion people, with mortality rates estimated at 1–2 million per year [...] Full article
(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)
Open AccessReview Invasive Candidiasis in Infants and Children: Recent Advances in Epidemiology, Diagnosis, and Treatment
J. Fungi 2019, 5(1), 11; https://doi.org/10.3390/jof5010011
Received: 5 December 2018 / Revised: 10 January 2019 / Accepted: 17 January 2019 / Published: 24 January 2019
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Abstract
This paper reviews recent advances in three selected areas of pediatric invasive candidiasis: epidemiology, diagnosis, and treatment. Although the epidemiological trends of pediatric invasive candidiasis illustrate a declining incidence, this infection still carries a heavy burden of mortality and morbidity that warrants a [...] Read more.
This paper reviews recent advances in three selected areas of pediatric invasive candidiasis: epidemiology, diagnosis, and treatment. Although the epidemiological trends of pediatric invasive candidiasis illustrate a declining incidence, this infection still carries a heavy burden of mortality and morbidity that warrants a high index of clinical suspicion, the need for rapid diagnostic systems, and the early initiation of antifungal therapy. The development of non-culture-based technologies, such as the T2Candida system and (1→3)-β-d-glucan detection assay, offers the potential for early laboratory detection of candidemia and CNS candidiasis, respectively. Among the complications of disseminated candidiasis in infants and children, hematogenous disseminated Candida meningoencephalitis (HCME) is an important cause of neurological morbidity. Detection of (1→3)-β-d-glucan in cerebrospinal fluid serves as an early diagnostic indicator and an important biomarker of therapeutic response. The recently reported pharmacokinetic data of liposomal amphotericin B in children demonstrate dose–exposure relationships similar to those in adults. The recently completed randomized clinical trial of micafungin versus deoxycholate amphotericin B in the treatment of neonatal candidemia provides further safety data for an echinocandin in this clinical setting. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts) Printed Edition available
Open AccessReview The ‘Amoeboid Predator-Fungal Animal Virulence’ Hypothesis
J. Fungi 2019, 5(1), 10; https://doi.org/10.3390/jof5010010
Received: 26 December 2018 / Revised: 15 January 2019 / Accepted: 19 January 2019 / Published: 21 January 2019
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Abstract
The observation that some aspects of amoeba-fungal interactions resemble animal phagocytic cell-fungal interactions, together with the finding that amoeba passage can enhance the virulence of some pathogenic fungi, has stimulated interest in the amoeba as a model system for the study of fungal [...] Read more.
The observation that some aspects of amoeba-fungal interactions resemble animal phagocytic cell-fungal interactions, together with the finding that amoeba passage can enhance the virulence of some pathogenic fungi, has stimulated interest in the amoeba as a model system for the study of fungal virulence. Amoeba provide a relatively easy and cheap model system where multiple variables can be controlled for the study of fungi-protozoal (amoeba) interactions. Consequently, there have been significant efforts to study fungal–amoeba interactions in the laboratory, which have already provided new insights into the origin of fungal virulence as well as suggested new avenues for experimentation. In this essay we review the available literature, which highlights the varied nature of amoeba-fungal interactions and suggests some unsolved questions that are potential areas for future investigation. Overall, results from multiple independent groups support the ‘amoeboid predator–fungal animal virulence hypothesis’, which posits that fungal cell predation by amoeba can select for traits that also function during animal infection to promote their survival and thus contribute to virulence. Full article
(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)
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Open AccessReview New Concepts in Diagnostics for Invasive Mycoses: Non-Culture-Based Methodologies
J. Fungi 2019, 5(1), 9; https://doi.org/10.3390/jof5010009
Received: 11 December 2018 / Revised: 14 January 2019 / Accepted: 15 January 2019 / Published: 17 January 2019
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Abstract
Non-culture-based diagnostics have been developed to help establish an early diagnosis of invasive fungal infection. Studies have shown that these tests can significantly impact the diagnosis of infection in high risk patients. Aspergillus galactomannan EIA testing is well-recognized as an important adjunct to [...] Read more.
Non-culture-based diagnostics have been developed to help establish an early diagnosis of invasive fungal infection. Studies have shown that these tests can significantly impact the diagnosis of infection in high risk patients. Aspergillus galactomannan EIA testing is well-recognized as an important adjunct to the diagnosis of invasive aspergillosis and can be detected in serum, bronchoalveolar lavage and other fluids. Galactomannan testing used along with PCR testing has been shown to be effective when integrated into care paths for high risk patients for both diagnoses and as a surrogate marker for outcome when used in serial testing. Beta-d-glucan assays are non-specific for several fungal genera including Aspergillus and Candida and in high risk patients have been an important tool to augment the diagnosis. Lateral flow technology using monoclonal antibodies to Aspergillus are available that allow rapid testing of clinical samples. While standard PCR for Candida remains investigational, T2 magnetic resonance allows for the rapid diagnosis of Candida species from blood cultures. Aspergillus PCR has been extensively validated with standardized approaches established for these methods and will be included in the diagnostic criteria in the revised European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC-MSG) definitions. Finally, these non-culture-based tests can be used in combination to significantly increase the detection of invasive mycoses with the ultimate aim of establishing an early diagnosis of infection. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts) Printed Edition available
Open AccessReview Sporotrichosis In Immunocompromised Hosts
J. Fungi 2019, 5(1), 8; https://doi.org/10.3390/jof5010008
Received: 3 December 2018 / Revised: 7 January 2019 / Accepted: 7 January 2019 / Published: 11 January 2019
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Abstract
Sporotrichosis is a global implantation or subcutaneous mycosis caused by several members of the genus Sporothrix, a thermo-dimorphic fungus. This disease may also depict an endemic profile, especially in tropical to subtropical zones around the world. Interestingly, sporotrichosis is an anthropozoonotic disease [...] Read more.
Sporotrichosis is a global implantation or subcutaneous mycosis caused by several members of the genus Sporothrix, a thermo-dimorphic fungus. This disease may also depict an endemic profile, especially in tropical to subtropical zones around the world. Interestingly, sporotrichosis is an anthropozoonotic disease that may be transmitted to humans by plants or by animals, especially cats. It may be associated with rather isolated or clustered cases but also with outbreaks in different periods and geographic regions. Usually, sporotrichosis affects immunocompetent hosts, presenting a chronic to subacute evolution course. Less frequently, sporotrichosis may be acquired by inhalation, leading to disseminated clinical forms. Both modes of infection may occur in immunocompromised patients, especially associated with human immunodeficiency virus (HIV) infection, but also diabetes mellitus, chronic alcoholism, steroids, anti-TNF treatment, hematologic cancer and transplanted patients. Similar to other endemic mycoses caused by dimorphic fungi, sporotrichosis in immunocompromised hosts may be associated with rather more severe clinical courses, larger fungal burden and longer periods of systemic antifungal therapy. A prolonged outbreak of cat-transmitted sporotrichosis is in progress in Brazil and potentially crossing the border to neighboring countries. This huge outbreak involves thousands of human and cats, including immunocompromised subjects affected by HIV and FIV (feline immunodeficiency virus), respectively. We reviewed the main epidemiologic, clinical, diagnostic and therapeutic aspects of sporotrichosis in immunocompromised hosts. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts) Printed Edition available
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Open AccessArticle Proteomic Analysis of the Responses of Candida albicans during Infection of Galleria mellonella Larvae
J. Fungi 2019, 5(1), 7; https://doi.org/10.3390/jof5010007
Received: 12 December 2018 / Revised: 8 January 2019 / Accepted: 9 January 2019 / Published: 11 January 2019
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Abstract
This study assessed the development of disseminated candidiasis within Galleria mellonella larvae and characterized the proteomic responses of Candida albicans to larval hemolymph. Infection of larvae with an inoculum of 1 × 106 yeast cells reduced larval viability 24 (53.33 ± 3.33%), [...] Read more.
This study assessed the development of disseminated candidiasis within Galleria mellonella larvae and characterized the proteomic responses of Candida albicans to larval hemolymph. Infection of larvae with an inoculum of 1 × 106 yeast cells reduced larval viability 24 (53.33 ± 3.33%), 48 (33.33 ± 3.33%) and 72 (6.66 ± 3.33%) h post infection. C. albicans infection quickly disseminated from the site of inoculation and the presence of yeast and hyphal forms were found in nodules extracted from infected larvae at 6 and 24 h. A range of proteins secreted during infection of G. mellonella by C. albicans were detected in larval hemolymph and these were enriched for biological processes such as interaction with host and pathogenesis. The candicidal activity of hemolymph after immediate incubation of yeast cells resulted in a decrease in yeast cell viability (0.23 ± 0.03 × 106 yeast cells/mL), p < 0.05) as compared to control (0.99 ± 0.01 × 106 yeast cells/mL). C. albicans responded to incubation in hemolymph ex vivo by the induction of an oxidative stress response, a decrease in proteins associated with protein synthesis and an increase in glycolytic proteins. The results presented here indicate that C. albicans can overcome the fungicidal activity of hemolymph by altering protein synthesis and cellular respiration, and commence invasion and dissemination throughout the host. Full article
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Open AccessEditorial Acknowledgement to Reviewers of Journal of Fungi in 2018
J. Fungi 2019, 5(1), 6; https://doi.org/10.3390/jof5010006
Published: 9 January 2019
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Abstract
Rigorous peer-review is the corner-stone of high-quality academic publishing [...] Full article
Open AccessArticle In Vitro and In Vivo Evaluation of Voriconazole-Containing Antifungal Combinations against Mucorales Using a Galleria mellonella Model of Mucormycosis
J. Fungi 2019, 5(1), 5; https://doi.org/10.3390/jof5010005
Received: 2 December 2018 / Revised: 22 December 2018 / Accepted: 6 January 2019 / Published: 8 January 2019
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Abstract
Mucorales are resistant to most antifungals. Mucormycosis associated mortality is unacceptable and new treatment approaches are needed. The objectives of this work were (i) to evaluate the nature and intensity of the in vitro effect of three drugs combinations which included voriconazole (plus [...] Read more.
Mucorales are resistant to most antifungals. Mucormycosis associated mortality is unacceptable and new treatment approaches are needed. The objectives of this work were (i) to evaluate the nature and intensity of the in vitro effect of three drugs combinations which included voriconazole (plus amphotericin B, posaconazole and caspofungin) against 25 strains of six different Mucorales species; (ii) to evaluate a Galleria mellonella mucormycosis model; and (iii) to establish if any in vitro–in vivo correlation exists. As expected, amphotericin B and posaconazole were the most active drugs when tested alone. However, species-specific differences were found. The ΣFICs varied according to the used combination. Only five strains showed synergism when voriconazole was combined with posaconazole and three strains when combined with amphotericin B. Microscopic hyphae alteration were observed for some isolates when confronted against drugs combinations. Using a Galleria mellonella mucormycosis model, better survival was seen in voriconazole plus amphotericin B and plus caspofungin combined treatments when compared with AMB alone for R. microsporus. These survival improvements were obtained using a 32-fold lower amphotericin B doses when combined with VRC than when treated with the polyene alone. These lower antifungal doses emulate the antifungal concentrations where the microscopic hyphae alterations were seen. Full article
(This article belongs to the Special Issue Mucorales and Mucormycosis)
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Open AccessReview A Moldy Application of MALDI: MALDI-ToF Mass Spectrometry for Fungal Identification
J. Fungi 2019, 5(1), 4; https://doi.org/10.3390/jof5010004
Received: 15 November 2018 / Revised: 7 December 2018 / Accepted: 25 December 2018 / Published: 3 January 2019
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Abstract
As a result of its being inexpensive, easy to perform, fast and accurate, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) is quickly becoming the standard means of bacterial identification from cultures in clinical microbiology laboratories. Its adoption for routine identification of [...] Read more.
As a result of its being inexpensive, easy to perform, fast and accurate, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) is quickly becoming the standard means of bacterial identification from cultures in clinical microbiology laboratories. Its adoption for routine identification of yeasts and even dimorphic and filamentous fungi in cultures, while slower, is now being realized, with many of the same benefits as have been recognized on the bacterial side. In this review, the use of MALDI-ToF MS for identification of yeasts, and dimorphic and filamentous fungi grown in culture will be reviewed, with strengths and limitations addressed. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts) Printed Edition available
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Open AccessReview Immune Response of Galleria mellonella against Human Fungal Pathogens
J. Fungi 2019, 5(1), 3; https://doi.org/10.3390/jof5010003
Received: 12 November 2018 / Revised: 14 December 2018 / Accepted: 20 December 2018 / Published: 26 December 2018
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Abstract
In many aspects, the immune response against pathogens in insects is similar to the innate immunity in mammals. This has caused a strong interest in the scientific community for the use of this model in research of host–pathogen interactions. In recent years, the [...] Read more.
In many aspects, the immune response against pathogens in insects is similar to the innate immunity in mammals. This has caused a strong interest in the scientific community for the use of this model in research of host–pathogen interactions. In recent years, the use of Galleria mellonella larvae, an insect belonging to the Lepidoptera order, has emerged as an excellent model to study the virulence of human pathogens. It is a model that offers many advantages; for example, it is easy to handle and establish in every laboratory, the larvae have a low cost, and they tolerate a wide range of temperatures, including human temperature 37 °C. The immune response of G. mellonella is innate and is divided into a cellular component (hemocytes) and humoral component (antimicrobial peptides, lytic enzymes, and peptides and melanin) that work together against different intruders. It has been shown that the immune response of this insect has a great specificity and has the ability to distinguish between different classes of microorganisms. In this review, we delve into the different components of the innate immune response of Galleria mellonella, and how these components manifest in the infection of fungal pathogens including Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, and Histoplasma capsulatum. Full article
(This article belongs to the Special Issue Alternative Models for the Study of Fungal Host-Pathogen Interactions)
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Open AccessReview Paracoccidioidomycosis in Immunocompromised Patients: A Literature Review
J. Fungi 2019, 5(1), 2; https://doi.org/10.3390/jof5010002
Received: 14 November 2018 / Revised: 9 December 2018 / Accepted: 21 December 2018 / Published: 26 December 2018
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Abstract
Paracoccidioidomycosis (PCM) is an endemic mycosis found in Latin America that causes systemic disease mostly in immunocompetent hosts. A small percentage of PCM occurs in immunocompromised patients where low clinical suspicion of the infection, late diagnosis, and uncertainties about its management are factors [...] Read more.
Paracoccidioidomycosis (PCM) is an endemic mycosis found in Latin America that causes systemic disease mostly in immunocompetent hosts. A small percentage of PCM occurs in immunocompromised patients where low clinical suspicion of the infection, late diagnosis, and uncertainties about its management are factors that negatively impact their outcomes. We conducted a literature review searching reports on PCM associated to HIV, cancer, maligned hemopathies, solid organ transplantation, and immunotherapies, in order to check for peculiarities in terms of natural history and challenges in the clinical management of PCM in this population. HIV patients with PCM usually had low T CD4+ cell counts, pulmonary and lymph nodes involvement, and a poorer prognosis (≈50% mortality). Most of the patients with PCM and cancer had carcinoma of the respiratory tract. Among maligned hemopathies, PCM was more often related to lymphoma. In general, PCM prognosis in patients with malignant diseases was related to the cancer stage. PCM in transplant recipients was mostly associated with the late phase of kidney transplantation, with a high mortality rate (44%). Despite being uncommon, reactivation of latent PCM may take place in the setting of immunocompromised patients exhibiting clinical particularities and it carries higher mortality rates than normal hosts. Full article
(This article belongs to the Special Issue Fungal Infections in Immunocompromised Hosts) Printed Edition available
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Open AccessArticle Deletion of ptn1, a PTEN/TEP1 Orthologue, in Ustilago maydis Reduces Pathogenicity and Teliospore Development
J. Fungi 2019, 5(1), 1; https://doi.org/10.3390/jof5010001
Received: 28 November 2018 / Revised: 13 December 2018 / Accepted: 19 December 2018 / Published: 20 December 2018
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Abstract
The PTEN/PI3K/mTOR signal transduction pathway is involved in the regulation of biological processes such as metabolism, cell growth, cell proliferation, and apoptosis. This pathway has been extensively studied in mammals, leading to the conclusion that PTEN is a major tumor suppressor gene. PTEN [...] Read more.
The PTEN/PI3K/mTOR signal transduction pathway is involved in the regulation of biological processes such as metabolism, cell growth, cell proliferation, and apoptosis. This pathway has been extensively studied in mammals, leading to the conclusion that PTEN is a major tumor suppressor gene. PTEN orthologues have been characterized in a variety of organisms, both vertebrates and non-vertebrates, and studies of the associated PTEN/PI3K/mTOR pathway indicate that it is widely conserved. Studies in fungal systems indicated a role of PTEN in fungal defense mechanisms in Candida albicans, and in the developmental process of sporulation in Saccharomyces cerevisiae. The present study was aimed at investigating the role of the PTEN ortholog, ptn1, in Ustilago maydis, the pathogen of maize. U. maydis ptn1 mutant strains where ptn1 gene is deleted or overexpressed were examined for phenotypes associate with mating, virulence and spore formation. While the overexpression of ptn1 had no substantial effects on virulence, ptn1 deletion strains showed slight reductions in mating efficiency and significant reductions in virulence; tumor formation on stem and/or leaves were severely reduced. Moreover, tumors, when present, had significantly lower levels of mature teliospores, and the percent germination of such spores was similarly reduced. Thus, ptn1 is required for these important aspects of virulence in this fungus. Full article
(This article belongs to the Special Issue Regulation of Fungal Morphogenesis and Gene Expression)
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