Open AccessReview
The Crucial Role of Biofilms in Cryptococcus neoformans Survival within Macrophages and Colonization of the Central Nervous System
J. Fungi 2017, 3(1), 10; doi:10.3390/jof3010010 (registering DOI) -
Abstract
Cryptococcus neoformans is an encapsulated yeast-like fungus capable of causing life threatening meningoencephalitis in patients with impaired immunity. This microbe primarily infects the host via inhalation but has the ability to disseminate to the central nervous system (CNS) either as a single cell
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Cryptococcus neoformans is an encapsulated yeast-like fungus capable of causing life threatening meningoencephalitis in patients with impaired immunity. This microbe primarily infects the host via inhalation but has the ability to disseminate to the central nervous system (CNS) either as a single cell or inside of macrophages. Upon traversing the blood brain barrier, C. neoformans has the capacity to form biofilm-like structures known as cryptococcomas. Hence, we will discuss the C. neoformans elements contributing to biofilm formation including the fungus’ ability to survive in the acidic environment of a macrophage phagosome and inside of the CNS. The purpose of this mini-review is to instill fresh interest in understanding the importance of biofilms on fungal pathogenesis. Full article
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Open AccessArticle
Combinatorial Biosynthesis of Novel Multi-Hydroxy Carotenoids in the Red Yeast Xanthophyllomyces dendrorhous
J. Fungi 2017, 3(1), 9; doi:10.3390/jof3010009 -
Abstract
The red yeast Xanthophyllomyces dendrorhous is an established platform for the synthesis of carotenoids. It was used for the generation of novel multi oxygenated carotenoid structures. This was achieved by a combinatorial approach starting with the selection of a β-carotene accumulating mutant, stepwise
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The red yeast Xanthophyllomyces dendrorhous is an established platform for the synthesis of carotenoids. It was used for the generation of novel multi oxygenated carotenoid structures. This was achieved by a combinatorial approach starting with the selection of a β-carotene accumulating mutant, stepwise pathway engineering by integration of three microbial genes into the genome and finally the chemical reduction of the resulting 4,4’-diketo-nostoxanthin (2,3,2’,3’-tetrahydroxy-4,4’-diketo-β-carotene) and 4-keto-nostoxanthin (2,3,2’,3’-tetrahydroxy-4-monoketo-β-carotene). Both keto carotenoids and the resulting 4,4’-dihydroxy-nostoxanthin (2,3,4,2’,3’,4’-hexahydroxy-β-carotene) and 4-hydroxy-nostoxanthin (2,3,4,2’3’-pentahydroxy-β-carotene) were separated by high-performance liquid chromatography (HPLC) and analyzed by mass spectrometry. Their molecular masses and fragmentation patterns allowed the unequivocal identification of all four carotenoids. Full article
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Open AccessReview
Candida Species Biofilms’ Antifungal Resistance
J. Fungi 2017, 3(1), 8; doi:10.3390/jof3010008 -
Abstract
Candida infections (candidiasis) are the most prevalent opportunistic fungal infection on humans and, as such, a major public health problem. In recent decades, candidiasis has been associated to Candida species other than Candida albicans. Moreover, biofilms have been considered the most prevalent
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Candida infections (candidiasis) are the most prevalent opportunistic fungal infection on humans and, as such, a major public health problem. In recent decades, candidiasis has been associated to Candida species other than Candida albicans. Moreover, biofilms have been considered the most prevalent growth form of Candida cells and a strong causative agent of the intensification of antifungal resistance. As yet, no specific resistance factor has been identified as the sole responsible for the increased recalcitrance to antifungal agents exhibited by biofilms. Instead, biofilm antifungal resistance is a complex multifactorial phenomenon, which still remains to be fully elucidated and understood. The different mechanisms, which may be responsible for the intrinsic resistance of Candida species biofilms, include the high density of cells within the biofilm, the growth and nutrient limitation, the effects of the biofilm matrix, the presence of persister cells, the antifungal resistance gene expression and the increase of sterols on the membrane of biofilm cells. Thus, this review intends to provide information on the recent advances about Candida species biofilm antifungal resistance and its implication on intensification of the candidiasis. Full article
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Open AccessReview
Global Aspects of Triazole Resistance in Aspergillus fumigatus with Focus on Latin American Countries
J. Fungi 2017, 3(1), 5; doi:10.3390/jof3010005 -
Abstract
Azole resistance in Aspergillus has emerged as an escalating problem in health care, and it has been detected in patients exposed, or not, to these drugs. It is known that azole antifungals are widely applied not only in clinical treatments for fungal infections,
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Azole resistance in Aspergillus has emerged as an escalating problem in health care, and it has been detected in patients exposed, or not, to these drugs. It is known that azole antifungals are widely applied not only in clinical treatments for fungal infections, but also as agricultural fungicides, resulting in a significant threat for human health. Although the number of cases of azole-resistant aspergillosis is still limited, various resistance mechanisms are described from clinical and environmental isolates. These mechanisms consist mainly of alterations in the target of azole action (CYP51A gene)—specifically on TR34/L98H and TR46/Y121F/T289A, which are responsible for over 90% of resistance cases. This review summarizes the epidemiology, management, and extension of azole resistance in A. fumigatus worldwide and its potential impact in Latin American countries, emphasizing its relevance to clinical practice. Full article
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Open AccessReview
Cutaneous Disseminated and Extracutaneous Sporotrichosis: Current Status of a Complex Disease
J. Fungi 2017, 3(1), 6; doi:10.3390/jof3010006 -
Abstract
Sporotrichosis is an implantation or inoculation mycosis caused by species of Sporothrix schenckii complex; its main manifestations are limited to skin; however, cutaneous-disseminated, disseminated (visceral) and extracutaneous variants of sporotrichosis can be associated with immunosuppression, including HIV-AIDS, chronic alcoholism or more virulent strains.
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Sporotrichosis is an implantation or inoculation mycosis caused by species of Sporothrix schenckii complex; its main manifestations are limited to skin; however, cutaneous-disseminated, disseminated (visceral) and extracutaneous variants of sporotrichosis can be associated with immunosuppression, including HIV-AIDS, chronic alcoholism or more virulent strains. The most common extracutaneous form of sporotrichosis includes pulmonary, osteoarticular and meningeal. The laboratory diagnosis requires observing yeast forms and isolating the fungus; the two main causative agents are Sporothrix schenckii (ss) and Sporothrix brasiliensis. Antibody levels and species recognition by Polimerase Chain Reaction using biological samples or cultures are also useful. The treatment of choice for most cases is amphotericin B and subsequent itraconazole for maintenance therapy. Full article
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Open AccessArticle
Comparative Efficacies of Antimicrobial Catheter Lock Solutions for Fungal Biofilm Eradication in an in Vitro Model of Catheter-Related Fungemia
J. Fungi 2017, 3(1), 7; doi:10.3390/jof3010007 -
Abstract
Fungal catheter-related bloodstream infections (CRBSIs)—primarily due to Candida species—account for over 12% of all CRBSIs, and have been progressively increasing in prevalence. They present significant health and economic burdens, and high mortality rates. Antimicrobial catheter lock solutions are an important prophylactic option for
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Fungal catheter-related bloodstream infections (CRBSIs)—primarily due to Candida species—account for over 12% of all CRBSIs, and have been progressively increasing in prevalence. They present significant health and economic burdens, and high mortality rates. Antimicrobial catheter lock solutions are an important prophylactic option for preventing fungal CRBSIs. In this study, we compared the effectiveness of two FDA-approved catheter lock solutions (heparin and saline) and three experimental antimicrobial catheter lock solutions—30% citrate, taurolidine-citrate-heparin (TCH), and nitroglycerin-citrate-ethanol (NiCE)—in an in vitro model of catheters colonized by fungi. The fungi tested were five different strains of Candida clinical isolates from cancer patients who contracted CRBSIs. Time-to-biofilm-eradication was assessed in the model with 15, 30, and 60 min exposures to the lock solutions. Only the NiCE lock solution was able to fully eradicate all fungal biofilms within 60 min. Neither 30% citrate nor TCH was able to fully eradicate any of the Candida biofilms in this time frame. The NiCE lock solution was significantly superior to TCH in eradicating biofilms of five different Candida species (p = 0.002 for all). Full article
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Open AccessReview
Entomopathogenicity and Biological Attributes of Himalayan Treasured Fungus Ophiocordyceps sinensis (Yarsagumba)
J. Fungi 2017, 3(1), 4; doi:10.3390/jof3010004 -
Abstract
Members of the entomophagous fungi are considered very crucial in the fungal domain relative to their natural phenomenon and economic perspectives; however, inadequate knowledge of their mechanisms of interaction keeps them lagging behind in parallel studies of fungi associated with agro-ecology, forest pathology
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Members of the entomophagous fungi are considered very crucial in the fungal domain relative to their natural phenomenon and economic perspectives; however, inadequate knowledge of their mechanisms of interaction keeps them lagging behind in parallel studies of fungi associated with agro-ecology, forest pathology and medical biology. Ophiocordyceps sinensis (syn. Cordyceps sinensis), an intricate fungus-caterpillar complex after it parasitizes the larva of the moth, is a highly prized medicinal fungus known widely for ages due to its peculiar biochemical assets. Recent technological innovations have significantly contributed a great deal to profiling the variable clinical importance of this fungus and other related fungi with similar medicinal potential. However, a detailed mechanism behind fungal pathogenicity and fungal-insect interactions seems rather ambiguous and is poorly justified, demanding special attention. The goal of the present review is to divulge an update on the published data and provides promising insights on different biological events that have remained underemphasized in previous reviews on fungal biology with relation to life-history trade-offs, host specialization and selection pressures. The infection of larvae by a fungus is not a unique event in Cordyceps; hence, other fungal species are also reviewed for effective comparison. Conceivably, the rationale and approaches behind the inheritance of pharmacological abilities acquired and stored within the insect framework at a time when they are completely hijacked and consumed by fungal parasites, and the molecular mechanisms involved therein, are clearly documented. Full article
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Open AccessEditorial
Acknowledgement to Reviewers of Journal of Fungi in 2016
J. Fungi 2017, 3(1), 3; doi:10.3390/jof3010003 -
Abstract The editors of Journal of Fungi would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...] Full article
Open AccessReview
Biocontrol Properties of Basidiomycetes: An Overview
J. Fungi 2017, 3(1), 2; doi:10.3390/jof3010002 -
Abstract
In agriculture, there is an urgent need for alternate ecofriendly products to control plant diseases. These alternate products must possess preferable characteristics such as new modes of action, cost effectiveness, biodegradability, and target specificity. In the current scenario, studies on macrofungi have been
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In agriculture, there is an urgent need for alternate ecofriendly products to control plant diseases. These alternate products must possess preferable characteristics such as new modes of action, cost effectiveness, biodegradability, and target specificity. In the current scenario, studies on macrofungi have been an area of importance for scientists. Macrofungi grow prolifically and are found in many parts of the world. Basidiomycetes (mushrooms) flourish ubiquitously under warm and humid climates. Basidiomycetes are rich sources of natural antibiotics. The secondary metabolites produced by them possess antimicrobial, antitumor, and antioxidant properties. The present review discusses the potential role of Basidiomycetes as anti-phytofungal, anti-phytobacterial, anti-phytoviral, mosquito larvicidal, and nematicidal agents. Full article
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Open AccessReview
New Trends in Paracoccidioidomycosis Epidemiology
J. Fungi 2017, 3(1), 1; doi:10.3390/jof3010001 -
Abstract
Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America and more prevalent in South America. The disease is caused by the dimorphic fungus Paracoccidioides spp. whose major hosts are humans and armadillos. The fungus grows in soil and its infection is associated
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Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America and more prevalent in South America. The disease is caused by the dimorphic fungus Paracoccidioides spp. whose major hosts are humans and armadillos. The fungus grows in soil and its infection is associated with exposure to the rural environment and to agricultural activities, with a higher risk in coffee and tobacco plantations. Population studies assessing the reactivity to Paracoccidioides spp. antigens by intradermal reaction or serological tests have detected previous subclinical infections in a significant proportion of healthy individuals living in various endemic countries. Paracoccidioidomycosis-disease is manifested by a small minority of infected individuals. The risk of developing the disease and its type of clinical form are related to the personal and life style characteristics of infected individuals, including genetic background, age, sex, ethnicity, smoking habit, alcohol drinking, and eventual cellular immunosuppression. Brazil, Colombia, Venezuela, Argentina, and Ecuador have endemic areas that had already been defined in the 20th century. The incidence of paracoccidioidomycosis can be altered by climate phenomena and mainly by human migration and occupation of poorly explored territories. In Brazil, the endemy tends to expand towards the North and Center-West around the Amazon Region. Full article
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Open AccessReview
The Quest for a Vaccine Against Coccidioidomycosis: A Neglected Disease of the Americas
J. Fungi 2016, 2(4), 34; doi:10.3390/jof2040034 -
Abstract
Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of Coccidioides spp. This neglected disease has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S., Mexico, Central and South America. The incidence of this infection in California
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Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of Coccidioides spp. This neglected disease has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S., Mexico, Central and South America. The incidence of this infection in California and Arizona has been increasing over the past fifteen years. Several large cities are within the endemic region in the U.S. Coccidioidomycosis accounts for 25,000 hospital admissions per year in California. While most cases of coccidioidomycosis resolve spontaneously, up to 40% are severe enough to require anti-fungal treatment, and a significant number disseminate beyond the lungs. Disseminated infection involving the meninges is fatal without appropriate treatment. Infection with Coccidioides spp. is protective against a second infection, so vaccination seems biologically plausible. This review of efforts to develop a vaccine against coccidioidomycosis focuses on vaccine approaches and the difficulties in identifying protein antigen/adjuvant combinations that protect in experimental mouse models. Although the quest for a vaccine is still in the early stage, scientific efforts for vaccine development may pave the way for future success. Full article
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Open AccessEditorial
Special Issue: Novel Antifungal Drug Discovery
J. Fungi 2016, 2(4), 33; doi:10.3390/jof2040033 -
Abstract
This Special Issue is designed to highlight the latest research and development on new antifungal compounds with mechanisms of action different from the ones of polyenes, azoles, and echinocandins. The papers presented here highlight new pathways and targets that could be exploited for
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This Special Issue is designed to highlight the latest research and development on new antifungal compounds with mechanisms of action different from the ones of polyenes, azoles, and echinocandins. The papers presented here highlight new pathways and targets that could be exploited for the future development of new antifungal agents to be used alone or in combination with existing antifungals. A computational model for better predicting antifungal drug resistance is also presented. Full article
Open AccessEditorial
Special Issue “Aspergillus fumigatus: From Diagnosis to Therapy”
J. Fungi 2016, 2(4), 31; doi:10.3390/jof2040031 -
Abstract Aspergillus fumigatus is an enigmatic pathogen. Full article
Open AccessReview
Allergic Aspergillus Rhinosinusitis
J. Fungi 2016, 2(4), 32; doi:10.3390/jof2040032 -
Abstract
Allergic fungal rhinosinusitis (AFRS) is a unique variety of chronic polypoid rhinosinusitis usually in atopic individuals, characterized by presence of eosinophilic mucin and fungal hyphae in paranasal sinuses without invasion into surrounding mucosa. It has emerged as an important disease involving a large
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Allergic fungal rhinosinusitis (AFRS) is a unique variety of chronic polypoid rhinosinusitis usually in atopic individuals, characterized by presence of eosinophilic mucin and fungal hyphae in paranasal sinuses without invasion into surrounding mucosa. It has emerged as an important disease involving a large population across the world with geographic variation in incidence and epidemiology. The disease is surrounded by controversies regarding its definition and etiopathogenesis. A working group on “Fungal Sinusitis” under the International Society for Human and Animal Mycology (ISHAM) addressed some of those issues, but many questions remain unanswered. The descriptions of “eosinophilic fungal rhinosinusitis” (EFRS), “eosinophilic mucin rhinosinusitis” (EMRS) and mucosal invasion by hyphae in few patients have increased the problem to delineate the disease. Various hypotheses exist for etiopathogenesis of AFRS with considerable overlap, though recent extensive studies have made certain in depth understanding. The diagnosis of AFRS is a multi-disciplinary approach including the imaging, histopathology, mycology and immunological investigations. Though there is no uniform management protocol for AFRS, surgical clearing of the sinuses with steroid therapy are commonly practiced. The role of antifungal agents, leukotriene antagonists and immunomodulators is still questionable. The present review covers the controversies, recent advances in pathogenesis, diagnosis, and management of AFRS. Full article
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Open AccessArticle
A Quantitative Model to Estimate Drug Resistance in Pathogens
J. Fungi 2016, 2(4), 30; doi:10.3390/jof2040030 -
Abstract
Pneumocystis pneumonia (PCP) is an opportunistic infection that occurs in humans and other mammals with debilitated immune systems. These infections are caused by fungi in the genus Pneumocystis, which are not susceptible to standard antifungal agents. Despite decades of research and drug development,
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Pneumocystis pneumonia (PCP) is an opportunistic infection that occurs in humans and other mammals with debilitated immune systems. These infections are caused by fungi in the genus Pneumocystis, which are not susceptible to standard antifungal agents. Despite decades of research and drug development, the primary treatment and prophylaxis for PCP remains a combination of trimethoprim (TMP) and sulfamethoxazole (SMX) that targets two enzymes in folic acid biosynthesis, dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), respectively. There is growing evidence of emerging resistance by Pneumocystis jirovecii (the species that infects humans) to TMP-SMX associated with mutations in the targeted enzymes. In the present study, we report the development of an accurate quantitative model to predict changes in the binding affinity of inhibitors (Ki, IC50) to the mutated proteins. The model is based on evolutionary information and amino acid covariance analysis. Predicted changes in binding affinity upon mutations highly correlate with the experimentally measured data. While trained on Pneumocystis jirovecii DHFR/TMP data, the model shows similar or better performance when evaluated on the resistance data for a different inhibitor of PjDFHR, another drug/target pair (PjDHPS/SMX) and another organism (Staphylococcus aureus DHFR/TMP). Therefore, we anticipate that the developed prediction model will be useful in the evaluation of possible resistance of the newly sequenced variants of the pathogen and can be extended to other drug targets and organisms. Full article
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Open AccessReview
Virulence Factors as Targets for Anticryptococcal Therapy
J. Fungi 2016, 2(4), 29; doi:10.3390/jof2040029 -
Abstract
The global mortality due to cryptococcosis caused by Cryptococcus neoformans or C. gattii is unacceptably high. Currently available therapies are decades old and may be impacted by drug resistance. Therefore, the need for more effective antifungal drugs for cryptococcosis is evident. A number
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The global mortality due to cryptococcosis caused by Cryptococcus neoformans or C. gattii is unacceptably high. Currently available therapies are decades old and may be impacted by drug resistance. Therefore, the need for more effective antifungal drugs for cryptococcosis is evident. A number of Cryptococcus virulence factors have been studied in detail, providing crucial information about the fungal biology and putative molecular targets for antifungals. This review focuses on the use of well-described virulence factors of Cryptococcus as potential anticryptococcal agents. Full article
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Open AccessArticle
Phylogenetic Analysis of the Synnema-Producing Genus Synnemapestaloides
J. Fungi 2016, 2(4), 28; doi:10.3390/jof2040028 -
Abstract
Synnemapestaloides rhododendri, the type species of the genus Synnemapestaloides, is a pathogen of Rhododendron brachycarpum. This fungus produces six-celled conidia with appendages at both end cells, and are generated by annellidic conidiogenous cells on the synnema. These conidial structures are
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Synnemapestaloides rhododendri, the type species of the genus Synnemapestaloides, is a pathogen of Rhododendron brachycarpum. This fungus produces six-celled conidia with appendages at both end cells, and are generated by annellidic conidiogenous cells on the synnema. These conidial structures are similar to those of the genus Pestalotia. The monotypic genus Synnemapestaloides is currently classified in the family Amphisphaeriaceae solely based on conidial morphology. Here we demonstrate that Synnemapestaloides represents a distinct genus in the family Sporocadaceae (Amphisphaeriales) based on differences in the nucleotide sequences of the partial large subunit rDNA gene, the rDNA internal transcribed spacer, and the partial β-tubulin. The genus most closely related to Synnemapestaloides is Seimatosporium and the species most similar to Synnemapestaloides rhododendri is Seim. foliicola which produces short synnema-like conidiomata (sporodochia). These results demonstrate that Seim. foliicola should be transferred to Synnemapestaloides, and also demonstrate that Sporocadaceae can have synnematal in addition to pycnidial and acervular conidiomata. Full article
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Open AccessCorrection
Correction: Stewart, E.R.; Thompson, G.R. Treatment of Primary Pulmonary Aspergillosis: An Assessment of the Evidence. J. Fungi 2016, 2, 25.
J. Fungi 2016, 2(4), 27; doi:10.3390/jof2040027 -
Abstract The authors of the published paper [1] would like to correct Table 1.[...] Full article
Open AccessReview
New Horizons in Antifungal Therapy
J. Fungi 2016, 2(4), 26; doi:10.3390/jof2040026 -
Abstract
Recent investigations have yielded both profound insights into the mechanisms required by pathogenic fungi for virulence within the human host, as well as novel potential targets for antifungal therapeutics. Some of these studies have resulted in the identification of novel compounds that act
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Recent investigations have yielded both profound insights into the mechanisms required by pathogenic fungi for virulence within the human host, as well as novel potential targets for antifungal therapeutics. Some of these studies have resulted in the identification of novel compounds that act against these pathways and also demonstrate potent antifungal activity. However, considerable effort is required to move from pre-clinical compound testing to true clinical trials, a necessary step toward ultimately bringing new drugs to market. The rising incidence of invasive fungal infections mandates continued efforts to identify new strategies for antifungal therapy. Moreover, these life-threatening infections often occur in our most vulnerable patient populations. In addition to finding completely novel antifungal compounds, there is also a renewed effort to redirect existing drugs for use as antifungal agents. Several recent screens have identified potent antifungal activity in compounds previously indicated for other uses in humans. Together, the combined efforts of academic investigators and the pharmaceutical industry is resulting in exciting new possibilities for the treatment of invasive fungal infections. Full article
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Open AccessReview
Treatment of Primary Pulmonary Aspergillosis: An Assessment of the Evidence
J. Fungi 2016, 2(3), 25; doi:10.3390/jof2030025 -
Abstract
Aspergillus spp. are a group of filamentous molds that were first described due to a perceived similarity to an aspergillum, or liturgical device used to sprinkle holy water, when viewed under a microscope. Although commonly inhaled due to their ubiquitous nature within the
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Aspergillus spp. are a group of filamentous molds that were first described due to a perceived similarity to an aspergillum, or liturgical device used to sprinkle holy water, when viewed under a microscope. Although commonly inhaled due to their ubiquitous nature within the environment, an invasive fungal infection (IFI) is a rare outcome that is often reserved for those patients who are immunocompromised. Given the potential for significant morbidity and mortality within this patient population from IFI due to Aspergillus spp., along with the rise in the use of therapies that confer immunosuppression, there is an increasing need for appropriate initial clinical suspicion leading to accurate diagnosis and effective treatment. Voriconazole remains the first line agent for therapy; however, the use of polyenes, novel triazole agents, or voriconazole in combination with an echinocandin may also be utilized. Consideration as to which particular agent and for what duration should be made in the individual context for each patient based upon underlying immunosuppression, comorbidities, and overall tolerance of therapy. Full article