9th Advances Against Aspergillosis and Mucormycosis

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

Deadline for manuscript submissions: closed (1 May 2020) | Viewed by 55383

Special Issue Editors


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Guest Editor
Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Schöpfstraße 41, 6020 Innsbruck, Austria
Interests: mycology; bacteriology; hospital hygiene
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Guest Editor
California Institute for Medical Research, 2260 Clove Dr, San Jose, CA 95128, USA
Interests: intermicrobial interactions; drug discovery
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Guest Editor
Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
Interests: chronic pulmonary aspergillosis; clinical trials; antifungal agents; pathogenesis; immunotherapy; invasive aspergillosis
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Guest Editor
Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
Interests: Aspergillus fumigatus hyphal growth; septation; drug resistance and stress response mechanisms

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Guest Editor
Infectious Diseases Service, Department of Medicine, and Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland
Interests: mechanisms of resistance in Aspergillus, Candida and Mucorales; epidemiology of invasive fungal infections; novel diagnostic approaches of invasive fungal infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues

We are excited to once again assemble many of the leading clinicians and scientists from around the world for the 9th Advances Against Aspergillosis and Mucormycosis conference, to take place in Lugano, Switzerland from 27 to 29 February 2020.

This conference has now clearly established itself as the premier forum for discussion of all aspects of Aspergillus and Mucorales infection and research. The Aspergillus and Mucorales fields continue in a state of rapid advancement in translational, immunologic, epidemiologic, diagnostic and therapeutic research.

We are pleased to announce the publication of a Conference Supplement, including papers from the invited speakers, in the Journal of Fungi. There are 5 Guest Editors, drawn from the faculty, who will be leading the 10th such Supplement. These Supplements are one of the foundations of the repository of knowledge about these microbes.

This meeting is another chance to gather the world’s aspergillosis and mucormycosis experts in one venue. A fundamental tenet of this colloquium continues to be to engender collaborative relationships amongst clinicians, scientists, and industry to further advance the field.

When this 9th meeting convenes, it will represent the 18th year of Advances Against Aspergillosis activity. All previous 8 international meetings were overwhelmingly successful, with attendance varying from 334 to 533, from 28 to 49 countries, with approximately 200 submitted abstracts, for each meeting.

Continuing education credit will be arranged through the Royal College of Physicians in London, which will provide appropriate CPD and CME credit for participants.

The Scientific Committee membership and the Program are available at: www.AAAM2020.org

David A. Stevens
William J. Steinbach
David W. Denning

AAAM2020 Organizers

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

  • Aspergillosis
  • Mucormycosis

Published Papers (14 papers)

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Editorial

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4 pages, 152 KiB  
Editorial
Advances against Aspergillosis and Mucormycosis
by David A. Stevens
J. Fungi 2020, 6(4), 358; https://doi.org/10.3390/jof6040358 - 11 Dec 2020
Viewed by 1767
Abstract
The 9th meeting of Advances Against Aspergillosis in beautiful Lugano, Switzerland clearly had the most drama of any of the previous meetings, exceeding even the 1st one, in San Francisco, when we, the Co-Organizers, weren’t sure that although we had a great educational [...] Read more.
The 9th meeting of Advances Against Aspergillosis in beautiful Lugano, Switzerland clearly had the most drama of any of the previous meetings, exceeding even the 1st one, in San Francisco, when we, the Co-Organizers, weren’t sure that although we had a great educational idea, and had put together a great list of speakers and topics, we might have few attendees, and go bankrupt! (The story of the birth efforts in initiating these meetings is described, for the historical record [...] Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)

Research

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25 pages, 4624 KiB  
Article
Aspergillus Is Inhibited by Pseudomonas aeruginosa Volatiles
by Hasan Nazik, Gabriele Sass, Eric Déziel and David A. Stevens
J. Fungi 2020, 6(3), 118; https://doi.org/10.3390/jof6030118 - 25 Jul 2020
Cited by 15 | Viewed by 3260
Abstract
Background: Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) compete with each other for nutrients and survival in natural environments, and have been extensively studied because of their intermicrobial interactions in the human microbiome. These are the principal microbes infecting immunocompromised patients and persons [...] Read more.
Background: Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) compete with each other for nutrients and survival in natural environments, and have been extensively studied because of their intermicrobial interactions in the human microbiome. These are the principal microbes infecting immunocompromised patients and persons with cystic fibrosis, particularly the airways. These intermicrobial studies have largely been conducted in liquid medium or on agar, and thus focus on soluble or diffusible microbial products. Several key inhibitory molecules were defined in such studies. Methods: in the present report, we examine several methodologies which can be conveniently used to study the interaction of microbial volatiles, including capture methods and kinetics. Results: Pa volatiles inhibit Af, and the inhibitory mechanism appears to be the incorporation of the inhibitory molecules into the substrate nourishing the Af, rather than directly onto Af structures. We define by mass spectroscopy some specific volatile Pa products that can inhibit Af. Some of these molecules are selected for interest by the study of gene deletion mutants, producing a few Pa strains that were impaired in inhibition. We presumed the volatiles of these latter strains could be excluded from the search for inhibitors. Conclusion: the Pa inhibition of Af via a gaseous phase could be critical components in their competition, particularly in airways, where more direct contact may not be extensive. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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10 pages, 919 KiB  
Communication
Rhizoferrin Glycosylation in Rhizopus microsporus
by Anton Škríba, Rutuja Hiraji Patil, Petr Hubáček, Radim Dobiáš, Andrea Palyzová, Helena Marešová, Tomáš Pluháček and Vladimír Havlíček
J. Fungi 2020, 6(2), 89; https://doi.org/10.3390/jof6020089 - 18 Jun 2020
Cited by 10 | Viewed by 3207
Abstract
Rhizopus spp. are the most common etiological agents of mucormycosis, causing over 90% mortality in disseminated infections. The diagnosis relies on histopathology, culture, and/or polymerase chain reaction. For the first time, the glycosylation of rhizoferrin (RHF) was described in a Rhizopus microsporus clinical [...] Read more.
Rhizopus spp. are the most common etiological agents of mucormycosis, causing over 90% mortality in disseminated infections. The diagnosis relies on histopathology, culture, and/or polymerase chain reaction. For the first time, the glycosylation of rhizoferrin (RHF) was described in a Rhizopus microsporus clinical isolate by liquid chromatography and accurate tandem mass spectrometry. The fermentation broth lyophilizate contained 345.3 ± 13.5, 1.2 ± 0.03, and 0.03 ± 0.002 mg/g of RHF, imido-RHF, and bis-imido-RHF, respectively. Despite a considerable RHF secretion rate, we did not obtain conclusive RHF detection from a patient with disseminated mucormycosis caused by the same R. microsporus strain. We hypothesize that parallel antimycotic therapy, RHF biotransformation, and metabolism compromised the analysis. On the other hand, the full profile of posaconazole metabolites was retrieved by our in house software CycloBranch. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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Review

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11 pages, 1608 KiB  
Review
Updated EUCAST Clinical Breakpoints against Aspergillus, Implications for the Clinical Microbiology Laboratory
by Jesús Guinea
J. Fungi 2020, 6(4), 343; https://doi.org/10.3390/jof6040343 - 06 Dec 2020
Cited by 19 | Viewed by 3807
Abstract
Azole resistance poses a problem for the management of patients with invasive aspergillosis. Former species are in fact groups of closely related species (or complexes); cryptic species frequently show high antifungal resistance. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) Definitive Document (E.Def) [...] Read more.
Azole resistance poses a problem for the management of patients with invasive aspergillosis. Former species are in fact groups of closely related species (or complexes); cryptic species frequently show high antifungal resistance. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) Definitive Document (E.Def) 9.3.2 includes guidelines for antifungal susceptibility testing on Aspergillus spp. and clinical breakpoints for amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole against A. flavus, A. fumigatus, A. nidulans, A. niger, and A. terreus. New clinical breakpoints were released in February 2020 and one of the most relevant modifications was the definition of the new “susceptible, increased exposure” (formerly “intermediate”) category. Another relevant change was the adoption of the concept of area of technical uncertainty (ATU) that refers to problematic areas which involve uncertainty of susceptibility categorisation (e.g., when minimum inhibitory concentrations (MICs) for susceptible and resistant organisms overlap). To accommodate both the new “susceptible, increased exposure” category and the concept of ATU, MICs of azoles and amphotericin B that fall in the former “intermediate” category have been automatically categorized as either R (amphotericin B) or ATU (triazoles). Finally, EUCAST-AFST (Antifungal Susceptibility Testing) decided to adopt new breakpoints for less common species provided that the epidemiological cut-off value (ECOFF) is below or comparable to the breakpoint for the type species (A. fumigatus). Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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15 pages, 2621 KiB  
Review
Modeling Invasive Aspergillosis: How Close Are Predicted Antifungal Targets?
by Thomas J. Walsh, Ruta Petraitiene and Vidmantas Petraitis
J. Fungi 2020, 6(4), 198; https://doi.org/10.3390/jof6040198 - 30 Sep 2020
Cited by 3 | Viewed by 3598
Abstract
Animal model systems are a critical component of the process of discovery and development of new antifungal agents for treatment and prevention of invasive aspergillosis. The persistently neutropenic rabbit model of invasive pulmonary aspergillosis (IPA) has been a highly predictive system in identifying [...] Read more.
Animal model systems are a critical component of the process of discovery and development of new antifungal agents for treatment and prevention of invasive aspergillosis. The persistently neutropenic rabbit model of invasive pulmonary aspergillosis (IPA) has been a highly predictive system in identifying new antifungal agents for treatment and prevention of this frequently lethal infection. Since its initial development, the persistently neutropenic rabbit model of IPA has established a strong preclinical foundation for dosages, drug disposition, pharmacokinetics, safety, tolerability, and efficacy for deoxycholate amphotericin B, liposomal amphotericin B, amphotericin B lipid complex, amphotericin B colloidal dispersion, caspofungin, micafungin, anidulafungin, voriconazole, posaconazole, isavuconazole, and ibrexafungerp in treatment of patients with invasive aspergillosis. The findings of combination therapy with a mould-active triazole and an echinocandin in this rabbit model also predicted the outcome of the clinical trial for voriconazole plus anidulafungin for treatment of IPA. The plasma pharmacokinetic parameters and tissue disposition for most antifungal agents approximate those of humans in persistently neutropenic rabbits. Safety, particularly nephrotoxicity, has also been highly predictive in the rabbit model, as exemplified by the differential glomerular filtration rates observed in animals treated with deoxycholate amphotericin B, liposomal amphotericin B, amphotericin B lipid complex, and amphotericin B colloidal dispersion. A panel of validated outcome variables measures therapeutic outcome in the rabbit model: residual fungal burden, markers of organism-mediated pulmonary injury (lung weights and infarct scores), survival, and serum biomarkers. In selected antifungal studies, thoracic computerized tomography (CT) is also used with diagnostic imaging algorithms to measure therapeutic response of pulmonary infiltrates, which exhibit characteristic radiographic patterns, including nodules and halo signs. Further strengthening the predictive properties of the model, therapeutic response to successfully developed antifungal agents for treatment of IPA has been demonstrated over the past two decades by biomarkers of serum galactomannan and (1→3)-β-D-glucan with patterns of resolution, that closely mirror those documented responses in patients with IPA. The decision to move from laboratory to clinical trials should be predicated upon a portfolio of complementary and mutually validating preclinical laboratory animal models studies. Other model systems, including those in mice, rats, and guinea pigs, are also valuable tools in developing clinical protocols. Meticulous preclinical investigation of a candidate antifungal compound in a robust series of complementary laboratory animal models will optimize study design, de-risk clinical trials, and ensure tangible benefit to our most vulnerable immunocompromised patients with invasive aspergillosis. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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12 pages, 503 KiB  
Review
Mucorales Species and Macrophages
by Francisco E. Nicolás, Laura Murcia, Eusebio Navarro, María Isabel Navarro-Mendoza, Carlos Pérez-Arques and Victoriano Garre
J. Fungi 2020, 6(2), 94; https://doi.org/10.3390/jof6020094 - 26 Jun 2020
Cited by 39 | Viewed by 4774
Abstract
Mucormycosis is an emerging fungal infection caused by Mucorales with an unacceptable high mortality rate. Mucorales is a complex fungal group, including eleven different genera that can infect humans. This heterogeneity is associated with species-specific invasion pathways and responses to the host defense [...] Read more.
Mucormycosis is an emerging fungal infection caused by Mucorales with an unacceptable high mortality rate. Mucorales is a complex fungal group, including eleven different genera that can infect humans. This heterogeneity is associated with species-specific invasion pathways and responses to the host defense mechanisms. The host innate immune system plays a major role in preventing Mucorales growth and host invasion. In this system, macrophages are the main immune effector cells in controlling these fungi by rapid and efficient phagocytosis of the spores. However, Mucorales have evolved mechanisms to block phagosomal maturation and species-specific mechanisms to either survive as dormant spores inside the macrophage, as Rhizopus species, or geminate and escape, as Mucor species. Classical fungal models of mucormycosis, mostly Rhizopus, have made important contributions to elucidate key aspects of the interaction between Mucorales and macrophages, but they lack robust tools for genetic manipulation. The recent introduction of the genetically tractable Mucor circinelloides as a model of mucormycosis offers the possibility to analyze gene function. This has allowed the identification of regulatory pathways that control the fungal response to phagocytosis, including a non-canonical RNAi pathway (NCRIP) that regulates the expression of most genes regulated by phagocytosis. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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9 pages, 1150 KiB  
Review
Aspergillus fumigatus Protease Alkaline Protease 1 (Alp1): A New Therapeutic Target for Fungal Asthma
by Kirk M. Druey, Morgan McCullough and Ramaswamy Krishnan
J. Fungi 2020, 6(2), 88; https://doi.org/10.3390/jof6020088 - 16 Jun 2020
Cited by 12 | Viewed by 3427
Abstract
We review three recent findings that have fundamentally altered our understanding of causative mechanisms underlying fungal-related asthma. These mechanisms may be partially independent of host inflammatory processes but are strongly dependent upon the actions of Alp1 on lung structural cells. They entail (i) [...] Read more.
We review three recent findings that have fundamentally altered our understanding of causative mechanisms underlying fungal-related asthma. These mechanisms may be partially independent of host inflammatory processes but are strongly dependent upon the actions of Alp1 on lung structural cells. They entail (i) bronchial epithelial sensing of Alp1; (ii) Alp1-induced airway smooth muscle (ASM) contraction; (iii) Alp1-induced airflow obstruction. Collectively, these mechanisms point to Alp1 as a new target for intervention in fungal asthma. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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9 pages, 1102 KiB  
Review
Clinical Relevance and Characteristics of Aspergillus calidoustus and Other Aspergillus Species of Section Usti
by Emmanouil Glampedakis, Véronique Erard and Frederic Lamoth
J. Fungi 2020, 6(2), 84; https://doi.org/10.3390/jof6020084 - 12 Jun 2020
Cited by 9 | Viewed by 6034
Abstract
The Aspergilli of section Usti (group ustus) are represented by over 20 species, of which Aspergillus calidoustus is the most relevant human pathogen. Invasive aspergillosis (IA) caused by these fungi is rare but could represent an emerging issue among the expanding population [...] Read more.
The Aspergilli of section Usti (group ustus) are represented by over 20 species, of which Aspergillus calidoustus is the most relevant human pathogen. Invasive aspergillosis (IA) caused by these fungi is rare but could represent an emerging issue among the expanding population of patients with long-term immunosuppression receiving antifungal prophylaxis. Clinicians should be aware of this unusual type of IA, which often exhibits distinct clinical features, such as an insidious and prolonged course and a high occurrence of extra-pulmonary manifestations, such as skin/soft tissue or brain lesions. Moreover, these Aspergillus spp. pose a therapeutic challenge because of their decreased susceptibility to azole drugs. In this review, we outline the microbiological and clinical characteristics of IA due to Aspergillus spp. of section Usti and discuss the therapeutic options. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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22 pages, 1509 KiB  
Review
Review of Potential Pseudomonas Weaponry, Relevant to the Pseudomonas–Aspergillus Interplay, for the Mycology Community
by Paulami Chatterjee, Gabriele Sass, Wieslaw Swietnicki and David A. Stevens
J. Fungi 2020, 6(2), 81; https://doi.org/10.3390/jof6020081 - 06 Jun 2020
Cited by 31 | Viewed by 5331
Abstract
Pseudomonas aeruginosa is one of the most prominent opportunistic bacteria in airways of cystic fibrosis patients and in immunocompromised patients. These bacteria share the same polymicrobial niche with other microbes, such as the opportunistic fungus Aspergillus fumigatus. Their inter-kingdom interactions and diverse exchange [...] Read more.
Pseudomonas aeruginosa is one of the most prominent opportunistic bacteria in airways of cystic fibrosis patients and in immunocompromised patients. These bacteria share the same polymicrobial niche with other microbes, such as the opportunistic fungus Aspergillus fumigatus. Their inter-kingdom interactions and diverse exchange of secreted metabolites are responsible for how they both fare in competition for ecological niches. The outcomes of their contests likely determine persistent damage and degeneration of lung function. With a myriad of virulence factors and metabolites of promising antifungal activity, P. aeruginosa products or their derivatives may prove useful in prophylaxis and therapy against A. fumigatus. Quorum sensing underlies the primary virulence strategy of P. aeruginosa, which serves as cell–cell communication and ultimately leads to the production of multiple virulence factors. Understanding the quorum-sensing-related pathogenic mechanisms of P. aeruginosa is a first step for understanding intermicrobial competition. In this review, we provide a basic overview of some of the central virulence factors of P. aeruginosa that are regulated by quorum-sensing response pathways and briefly discuss the hitherto known antifungal properties of these virulence factors. This review also addresses the role of the bacterial secretion machinery regarding virulence factor secretion and maintenance of cell–cell communication. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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10 pages, 612 KiB  
Review
Airway Mycosis and the Regulation of Type 2 Immunity
by John Morgan Knight, Yifan Wu, Kelsey Mauk, Jill Weatherhead, Sara Anvari, Farrah Kheradmand and David B. Corry
J. Fungi 2020, 6(2), 74; https://doi.org/10.3390/jof6020074 - 29 May 2020
Cited by 3 | Viewed by 3466
Abstract
Filamentous fungi of the Aspergillus genus and others have long been linked to the induction of type 2 immunity that underlies IgE-mediated hypersensitivity responses. This unique immune response is characterized by the production of the allergy-associated T helper cell type 2 (Th2) and [...] Read more.
Filamentous fungi of the Aspergillus genus and others have long been linked to the induction of type 2 immunity that underlies IgE-mediated hypersensitivity responses. This unique immune response is characterized by the production of the allergy-associated T helper cell type 2 (Th2) and Th17 cytokines interleukin 4 (IL-4), IL-13, and IL-17 that drive IgE, eosinophilia, airway hyperresponsiveness and other manifestations of asthma. Proteinases secreted by filamentous fungi promote type 2 immunity, but the mechanism by which this occurs has long remained obscure. Through detailed biochemical analysis of household dust, microbiological dissection of human airway secretions, and extensive modeling in mice, our laboratory has assembled a detailed mechanistic description of how type 2 immunity evolves after exposure to fungi. In this review we summarize three key discoveries: (1) fungal proteinases drive the type 2 immune response; (2) the relationship between fungi, proteinases, and type 2 immunity is explained by airway mycosis, a form of non-invasive fungal infection of the airway lumen; and (3) the innate component of proteinase-driven type 2 immunity is mediated by cleavage of the clotting protein fibrinogen. Despite these advances, additional work is required to understand how Th2 and Th17 responses evolve and the role that non-filamentous fungi potentially play in allergic diseases. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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9 pages, 2436 KiB  
Review
Siderophore-Based Molecular Imaging of Fungal and Bacterial Infections—Current Status and Future Perspectives
by Milos Petrik, Joachim Pfister, Matthias Misslinger, Clemens Decristoforo and Hubertus Haas
J. Fungi 2020, 6(2), 73; https://doi.org/10.3390/jof6020073 - 29 May 2020
Cited by 30 | Viewed by 5548
Abstract
Invasive fungal infections such as aspergillosis are life-threatening diseases mainly affecting immuno-compromised patients. The diagnosis of fungal infections is difficult, lacking specificity and sensitivity. This review covers findings on the preclinical use of siderophores for the molecular imaging of infections. Siderophores are low [...] Read more.
Invasive fungal infections such as aspergillosis are life-threatening diseases mainly affecting immuno-compromised patients. The diagnosis of fungal infections is difficult, lacking specificity and sensitivity. This review covers findings on the preclinical use of siderophores for the molecular imaging of infections. Siderophores are low molecular mass chelators produced by bacteria and fungi to scavenge the essential metal iron. Replacing iron in siderophores by radionuclides such as gallium-68 allowed the targeted imaging of infection by positron emission tomography (PET). The proof of principle was the imaging of pulmonary Aspergillus fumigatus infection using [68Ga]Ga-triacetylfusarinine C. Recently, this approach was expanded to imaging of bacterial infections, i.e., with Pseudomonas aeruginosa. Moreover, the conjugation of siderophores and fluorescent dyes enabled the generation of hybrid imaging compounds, allowing the combination of PET and optical imaging. Nevertheless, the high potential of these imaging probes still awaits translation into clinics. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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17 pages, 482 KiB  
Review
Kids, Difficult Asthma and Fungus
by Andrew Bush
J. Fungi 2020, 6(2), 55; https://doi.org/10.3390/jof6020055 - 27 Apr 2020
Cited by 20 | Viewed by 4187
Abstract
Fungi have many potential roles in paediatric asthma, predominantly by being a source of allergens (severe asthma with fungal sensitization, SAFS), and also directly damaging the epithelial barrier and underlying tissue by releasing proteolytic enzymes (fungal bronchitis). The umbrella term ‘fungal asthma’ is [...] Read more.
Fungi have many potential roles in paediatric asthma, predominantly by being a source of allergens (severe asthma with fungal sensitization, SAFS), and also directly damaging the epithelial barrier and underlying tissue by releasing proteolytic enzymes (fungal bronchitis). The umbrella term ‘fungal asthma’ is proposed for these manifestations. Allergic bronchopulmonary aspergillosis (ABPA) is not a feature of childhood asthma, for unclear reasons. Diagnostic criteria for SAFS are based on sensitivity to fungal allergen(s) demonstrated either by skin prick test or specific IgE. In children, there are no exclusion criteria on total IgE levels or IgG precipitins because of the rarity of ABPA. Diagnostic criteria for fungal bronchitis are much less well established. Data in adults and children suggest SAFS is associated with worse asthma control and greater susceptibility to asthma attacks than non-sensitized patients. The data on whether anti-fungal therapy is beneficial are conflicting. The pathophysiology of SAFS is unclear, but the epithelial alarmin interleukin-33 is implicated. However, whether individual fungi have different pathobiologies is unclear. There are many unanswered questions needing further research, including how fungi interact with other allergens, bacteria, and viruses, and what optimal therapy should be, including whether anti-neutrophilic strategies, such as macrolides, should be used. Considerable further research is needed to unravel the complex roles of different fungi in severe asthma. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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Other

9 pages, 1233 KiB  
Brief Report
Modeling Approaches Reveal New Regulatory Networks in Aspergillus fumigatus Metabolism
by Enzo Acerbi, Marcela Hortova-Kohoutkova, Tsokyi Choera, Nancy Keller, Jan Fric, Fabio Stella, Luigina Romani and Teresa Zelante
J. Fungi 2020, 6(3), 108; https://doi.org/10.3390/jof6030108 - 14 Jul 2020
Cited by 1 | Viewed by 2687
Abstract
Systems biology approaches are extensively used to model and reverse-engineer gene regulatory networks from experimental data. Indoleamine 2,3-dioxygenases (IDOs)—belonging in the heme dioxygenase family—degrade l-tryptophan to kynurenines. These enzymes are also responsible for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). [...] Read more.
Systems biology approaches are extensively used to model and reverse-engineer gene regulatory networks from experimental data. Indoleamine 2,3-dioxygenases (IDOs)—belonging in the heme dioxygenase family—degrade l-tryptophan to kynurenines. These enzymes are also responsible for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). As such, they are expressed by a variety of species, including fungi. Interestingly, Aspergillus may degrade l-tryptophan not only via IDO but also via alternative pathways. Deciphering the molecular interactions regulating tryptophan metabolism is particularly critical for novel drug target discovery designed to control pathogen determinants in invasive infections. Using continuous time Bayesian networks over a time-course gene expression dataset, we inferred the global regulatory network controlling l-tryptophan metabolism. The method unravels a possible novel approach to target fungal virulence factors during infection. Furthermore, this study represents the first application of continuous-time Bayesian networks as a gene network reconstruction method in Aspergillus metabolism. The experiment showed that the applied computational approach may improve the understanding of metabolic networks over traditional pathways. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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6 pages, 511 KiB  
Brief Report
International Society for Human and Animal Mycology (ISHAM)—New Initiatives
by Arunaloke Chakrabarti, Jacques F. Meis and Oliver A. Cornely
J. Fungi 2020, 6(3), 97; https://doi.org/10.3390/jof6030097 - 30 Jun 2020
Cited by 4 | Viewed by 2738
Abstract
Fungal infections have emerged as major threat to human beings. The world is not ready to face this formidable challenge due to limited awareness, insufficient laboratories, and difficulty in managing mycoses especially in developing countries. The International Society for Human and Animal Mycology [...] Read more.
Fungal infections have emerged as major threat to human beings. The world is not ready to face this formidable challenge due to limited awareness, insufficient laboratories, and difficulty in managing mycoses especially in developing countries. The International Society for Human and Animal Mycology (ISHAM) has undertaken several new initiatives to overcome these gaps, including a global outreach program with national affiliated mycology societies and other regional groups. ISHAM is working closely with the European Confederation of Medical Mycology (ECMM) and Global Action Fund for Fungal Infections (GAFFI) to enhance these efforts. The society has launched laboratory e-courses and is in the process of the development of clinical e-courses. ISHAM has partnered with regional conferences in South America and Asia by sponsoring international experts and young delegates. The society also supports young people from less developed countries to undergo training in laboratories of excellence. ISHAM facilitated the formation of the INFOCUS-Latin American Clinical Mycology Working Group (LATAM) and the Pan-African Mycology Working Group. The society appointed country ambassadors to facilitate coordination with national societies. Still, the task is enormous and ISHAM calls for strong advocacy and more coordinated activities to attract the attention of people from all disciplines to this neglected field. Full article
(This article belongs to the Special Issue 9th Advances Against Aspergillosis and Mucormycosis)
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