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Translational Science: Approaches to Reducing Burden Caused by Fungal Diseases
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Translational Science: Approaches to Reducing Burden Caused by Fungal Diseases

A special issue of Journal of Fungi (ISSN 2309-608X).

Deadline for manuscript submissions: closed (28 February 2018)

Special Issue Editor

Prof. Dr. Richard Calderone

E-Mail Website
Guest Editor
Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, 20057, USA
Interests: pathogenesis of human yeast infections; molecular pathogenesis; antifungals; drug resistance; bioinformatics; mitochondria
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

I have chosen author contributions for this Special Issue based on their translational implications that seek to reduce fungal burden. The Special Issue will be composed of 12 submitted papers (see attachment). The submitted papers will be organized in two parts, those being: 1) patients: Detection and therapies for the invasive fungal infections, candidiasis, aspergillosis and cryptococcosis; and 2) papers related to the host-fungal-commensal interface. Part 1 will include papers on the global incidence of fungal infections, patient susceptibility (genetic predisposition), antifungal susceptibilities among Candida species, PCR based methods of detection, immunotherapy, and prophylaxis antifungal therapy. Part 2 focuses upon the basic science of fungal pathogenesis and includes papers on microbiomes (2 papers), fungal-specific drug targets, microevolution of virulence, cytokine receptor signaling, and morphotype functions of C. neoformans. Part 2 papers were selected based on ideas that may have translational implications.

The subjects of Part 1 are based upon current understanding primarily of candidemia. There is now sufficient literature to discuss gene SNPs that identify high-risk patients. The fairly new PCR-based assay to aid in the diagnosis of invasive candidiasis will be discussed. Controversy exists about how to treat culture-negative invasive candidiasis; one suggestion is prophylaxis treatment with antifungals. Alternatives to drug treatment include immunotherapy.

In part 2, the microbiomes associated with candidiasis and aspergillosis will be featured. Exploitation of fungal-specific targets in new drug therapy will in part emphasize the bioinformatics approach to identify these targets. Another paper will explain the concept of microevolution that describes the conversion of avirulence to virulence within macrophages. Cell transitional growth has been the subject of numerous reviews. New data suggest that growth transitional types in C. neoformans have different functions in pathogenesis.

Prof. Dr. Richard Calderone
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • fungal pathogenesis
  • candidiasis, aspergillosis and cryptococcosis
  • fungal burden
  • fungal detection and and therapies
  • prophylaxis treatment
  • candidemia
  • Antifungal and vaccine development

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Published Papers (4 papers)

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Review

10 pages, 1132 KiB  
Review
T2 Magnetic Resonance Assay: Overview of Available Data and Clinical Implications
by Ioannis M. Zacharioudakis, Fainareti N. Zervou and Eleftherios Mylonakis
J. Fungi 2018, 4(2), 45; https://doi.org/10.3390/jof4020045 - 4 Apr 2018
Cited by 42 | Viewed by 7051
Abstract
Invasive candidiasis is a common healthcare-associated infection with a high mortality rate that can exceed 60% in cases of septic shock. Blood culture performance is far from ideal, due to the long time to positivity and suppression by antifungal agents. The T2 Magnetic [...] Read more.
Invasive candidiasis is a common healthcare-associated infection with a high mortality rate that can exceed 60% in cases of septic shock. Blood culture performance is far from ideal, due to the long time to positivity and suppression by antifungal agents. The T2 Magnetic Resonance (T2MR) assay is an FDA-approved qualitative molecular diagnostic method that can detect and speciate the 5 most common Candida spp.; namely, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Candida krusei, in approximately 5 h. In a multicenter clinical trial that included both a prospective and a contrived arm to represent the full range of clinically relevant concentrations of Candida spp., T2MR demonstrated a sensitivity and specificity of 91.1% and 98.1%, respectively. The utility of T2MR in candidemia depends on the prevalence of disease in each clinical setting. In intensive care units and other high-prevalence settings, the incorporation of T2MR in diagnostic algorithms is very appealing. T2MR is expected to allow timely initiation of antifungal therapy and help with anti-fungal stewardship. In low-prevalence settings, the positive predictive value of T2MR might not be enough to justify initiation of antifungal treatment in itself. The performance of T2MR has not been studied in cases of deep-seated candidiasis. Despite some promising evidence in published clinical trials, further studies are needed to determine the performance of T2MR in invasive candidiasis without candidemia. Overall, experience with T2MR in everyday clinical practice is evolving but, in the right setting, this technology is expected to provide “actionable information” for the management of patients evaluated for candidemia. Full article
(This article belongs to the Special Issue Translational Science: Approaches to Reducing Burden Caused by Fungal Diseases)
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20 pages, 568 KiB  
Review
Patient Susceptibility to Candidiasis—A Potential for Adjunctive Immunotherapy
by Linda Davidson, Mihai G. Netea and Bart Jan Kullberg
J. Fungi 2018, 4(1), 9; https://doi.org/10.3390/jof4010009 - 9 Jan 2018
Cited by 24 | Viewed by 6375
Abstract
Candida spp. are colonizing fungi of human skin and mucosae of the gastrointestinal and genitourinary tract, present in 30–50% of healthy individuals in a population at any given moment. The host defense mechanisms prevent this commensal fungus from invading and causing disease. Loss [...] Read more.
Candida spp. are colonizing fungi of human skin and mucosae of the gastrointestinal and genitourinary tract, present in 30–50% of healthy individuals in a population at any given moment. The host defense mechanisms prevent this commensal fungus from invading and causing disease. Loss of skin or mucosal barrier function, microbiome imbalances, or defects of immune defense mechanisms can lead to an increased susceptibility to severe mucocutaneous or invasive candidiasis. A comprehensive understanding of the immune defense against Candida is essential for developing adjunctive immunotherapy. The important role of underlying genetic susceptibility to Candida infections has become apparent over the years. In most patients, the cause of increased susceptibility to fungal infections is complex, based on a combination of immune regulation gene polymorphisms together with other non-genetic predisposing factors. Identification of patients with an underlying genetic predisposition could help determine which patients could benefit from prophylactic antifungal treatment or adjunctive immunotherapy. This review will provide an overview of patient susceptibility to mucocutaneous and invasive candidiasis and the potential for adjunctive immunotherapy. Full article
(This article belongs to the Special Issue Translational Science: Approaches to Reducing Burden Caused by Fungal Diseases)
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Figure 1

2094 KiB  
Review
Morphology Changes in Human Fungal Pathogens upon Interaction with the Host
by Zhongming Li and Kirsten Nielsen
J. Fungi 2017, 3(4), 66; https://doi.org/10.3390/jof3040066 - 1 Dec 2017
Cited by 38 | Viewed by 8165
Abstract
Morphological changes are a very common and effective strategy for pathogens to survive in the mammalian host. During interactions with their host, human pathogenic fungi undergo an array of morphological changes that are tightly associated with virulence. Candida albicans switches between yeast cells [...] Read more.
Morphological changes are a very common and effective strategy for pathogens to survive in the mammalian host. During interactions with their host, human pathogenic fungi undergo an array of morphological changes that are tightly associated with virulence. Candida albicans switches between yeast cells and hyphae during infection. Thermally dimorphic pathogens, such as Histoplasma capsulatum and Blastomyces species transform from hyphal growth to yeast cells in response to host stimuli. Coccidioides and Pneumocystis species produce spherules and cysts, respectively, which allow for the production of offspring in a protected environment. Finally, Cryptococcus species suppress hyphal growth and instead produce an array of yeast cells—from large polyploid titan cells to micro cells. While the morphology changes produced by human fungal pathogens are diverse, they all allow for the pathogens to evade, manipulate, and overcome host immune defenses to cause disease. In this review, we summarize the morphology changes in human fungal pathogens—focusing on morphological features, stimuli, and mechanisms of formation in the host. Full article
(This article belongs to the Special Issue Translational Science: Approaches to Reducing Burden Caused by Fungal Diseases)
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1348 KiB  
Review
Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision
by Felix Bongomin, Sara Gago, Rita O. Oladele and David W. Denning
J. Fungi 2017, 3(4), 57; https://doi.org/10.3390/jof3040057 - 18 Oct 2017
Cited by 1887 | Viewed by 59250
Abstract
Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health [...] Read more.
Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health problems including asthma, AIDS, cancer, organ transplantation and corticosteroid therapies. Early accurate diagnosis allows prompt antifungal therapy; however this is often delayed or unavailable leading to death, serious chronic illness or blindness. Recent global estimates have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur annually. Since 2013, the Leading International Fungal Education (LIFE) portal has facilitated the estimation of the burden of serious fungal infections country by country for over 5.7 billion people (>80% of the world’s population). These studies have shown differences in the global burden between countries, within regions of the same country and between at risk populations. Here we interrogate the accuracy of these fungal infection burden estimates in the 43 published papers within the LIFE initiative. Full article
(This article belongs to the Special Issue Translational Science: Approaches to Reducing Burden Caused by Fungal Diseases)
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