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Aspergillus and Health 1.0
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Aspergillus and Health 1.0

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Public Health Microbiology".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 36541

Special Issue Editor

Dr. Raquel Sabino

E-Mail Website1 Website2
Guest Editor
Reference Unit for Parasitic and Fungal Infections, Department of Infectious Diseases, National Institute of Health, Av. Padre Cruz, 1649-016 Lisbon, Portugal
Interests: fungal infections diagnosis; Aspergillus; fungi; infectious diseases; fungal epidemiology and public health; antifungal resistance; molecular biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Aspergillus is the filamentous fungi more frequently associated with invasive fungal infection. According to the LIFE organization, more than 30 million patients are at risk for invasive aspergillosis and about 300,000 patients will develop the disease annually. Besides the high mortality rate in immunocompromised patients, significant pulmonary pathology is also associated with Aspergillus-induced allergic and asthmatic lung disease related to occupational exposure. An effective diagnosis is often complex and is still a challenge.  Molecular characterizations of Aspergillus have been contributing to the discovery of new etiological agents and to the knowledge of species distribution and their possible role in pathogenesis, especially regarding antifungal resistance and virulence. Antifungal susceptibility is highly variable among cryptic species, several of which show high in vitro minimal inhibitory concentrations to multiple antifungal drugs. Azole resistance has been increasing in prevalence in A. fumigatus isolates due to the development of acquired resistance caused by prophylaxis/treatment with antifungals, as well as to the use of agricultural azoles and consequent acquisition of resistant isolates from environmental origin, posing new challenges in therapeutic management. This special issue, titled “Aspergillus and Health,” aims to discuss these questions and present some of the most recent studies on this area.

Dr. Raquel Sabino
Guest Editor

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Keywords

  • Aspergillus
  • Aspergillosis
  • Diagnosis
  • Epidemiology
  • Antifungal resistance

Published Papers (12 papers)

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Editorial

Jump to: Research, Review

4 pages, 198 KiB  
Editorial
Aspergillus and Health
by Raquel Sabino
Microorganisms 2022, 10(3), 538; https://doi.org/10.3390/microorganisms10030538 - 28 Feb 2022
Cited by 1 | Viewed by 1782
Abstract
Among the filamentous fungi described as etiological agents of infection, Aspergillus is the most frequent agent of invasive mould disease, and it is associated with high mortality [...] Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)

Research

Jump to: Editorial, Review

14 pages, 2631 KiB  
Article
Effects of Aspergillus fumigatus Conidia on Apoptosis and Proliferation in an In Vitro Model of the Lung Microenvironment
by Hisako Kushima, Toshiyuki Tsunoda, Taichi Matsumoto, Yoshiaki Kinoshita, Koichi Izumikawa, Senji Shirasawa, Masaki Fujita and Hiroshi Ishii
Microorganisms 2021, 9(7), 1435; https://doi.org/10.3390/microorganisms9071435 - 2 Jul 2021
Cited by 2 | Viewed by 2508
Abstract
Background/Aim: Aspergillus is often detected in respiratory samples from patients with chronic respiratory diseases, including pulmonary fibrosis, suggesting that it can easily colonize the airways. To determine the role of Aspergillus colonization in pulmonary fibrosis, we cultured human lung epithelial A549 cells or [...] Read more.
Background/Aim: Aspergillus is often detected in respiratory samples from patients with chronic respiratory diseases, including pulmonary fibrosis, suggesting that it can easily colonize the airways. To determine the role of Aspergillus colonization in pulmonary fibrosis, we cultured human lung epithelial A549 cells or murine embryo fibroblast NIH/3T3 cells with Aspergillus conidia in 3D floating culture representing the microenvironment. Materials and Methods: Cells were cultured in two-dimensional (2D) and three-dimensional floating (3DF) culture with heat-inactivated Aspergillus fumigatus (AF) 293 conidia at an effector-to-target cell ratio of 1:10 (early-phase model) and 1:100 (colonization model), and RNA-sequencing and Western blots (WB) were performed. Results: AF293 conidia reduced A549 cell growth in 2D and 3DF cultures and induced apoptosis in A549 spheroids in 3DF culture. RNA-sequencing revealed the increased expression of genes associated with interferon-mediated antiviral responses including MX dymamin-like GTPase 1 (MX1). Interestingly, the decreased expression of genes associated with the cell cycle was observed with a high concentration of AF293 conidia. WB revealed that epithelial-mesenchymal transition was not involved. Notably, AF293 conidia increased NIH/3T3 growth only in 3DF culture without inducing an apoptotic reaction. RNA-sequencing revealed the increased expression of genes associated with interferon signalling, including MX2; however, the decreased expression of genes associated with the cell cycle was not observed. Conclusions: AF affects both apoptosis of epithelial cells and the growth of fibroblasts. A deeper understanding of the detailed mechanisms underlying Aspergillus-mediated signaling pathway in epithelial cells and fibroblasts will help us to understand the lung microenvironment. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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11 pages, 3643 KiB  
Article
Selective Flamingo Medium for the Isolation of Aspergillus fumigatus
by Jianhua Zhang, Alfons J. M. Debets, Paul E. Verweij and Sijmen E. Schoustra
Microorganisms 2021, 9(6), 1155; https://doi.org/10.3390/microorganisms9061155 - 27 May 2021
Cited by 2 | Viewed by 2954
Abstract
For various studies in the clinic as well as the environment, it is essential to be able to selectively isolate Aspergillus fumigatus from samples containing bacteria as well as various other fungi (mainly Mucorales). Six agar media were compared for effectiveness in selectively [...] Read more.
For various studies in the clinic as well as the environment, it is essential to be able to selectively isolate Aspergillus fumigatus from samples containing bacteria as well as various other fungi (mainly Mucorales). Six agar media were compared for effectiveness in selectively isolating Aspergillus fumigatus from agricultural plant waste, woodchip waste, green waste, soil, grass and air samples collected in The Netherlands at a 48 °C incubation. The Flamingo Medium incubated at 48 °C, provided the most effective condition for the isolation of A. fumigatus from environmental samples, since it effectively inhibited the growth of competing fungi (mainly Mucorales) present in the environmental samples. Flamingo Medium reduced the number of colonies of Mucorales species by 95% and recovered an average of 20−30% more A. fumigatus colonies compared to the other media. We further confirmed that Flamingo Medium can inhibit the growth of clinical Mucorales, which occasionally present in patient’s tissue and can also be used for clinical applications. We suggest the use of Flamingo Medium as an efficient method for the study of A. fumigatus from important environmental niches for which there is increasing interest. Additionally, it can also be used in the clinic to isolate A. fumigatus especially from tissue contaminated with Mucorales. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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11 pages, 1435 KiB  
Article
The Environmental Spread of Aspergillus terreus in Tyrol, Austria
by Anna-Maria Dietl, Roya Vahedi-Shahandashti, Carmen Kandelbauer, Bart Kraak, Michaela Lackner, Jos Houbraken and Cornelia Lass-Flörl
Microorganisms 2021, 9(3), 539; https://doi.org/10.3390/microorganisms9030539 - 5 Mar 2021
Cited by 7 | Viewed by 2687
Abstract
Fungal infections due to Aspergillus species have become a major cause of morbidity and mortality among immunocompromised patients. At the Medical University of Innsbruck, A. terreus and related species are the second most common causative agents of aspergillosis. In this one-year study we [...] Read more.
Fungal infections due to Aspergillus species have become a major cause of morbidity and mortality among immunocompromised patients. At the Medical University of Innsbruck, A. terreus and related species are the second most common causative agents of aspergillosis. In this one-year study we collected environmental samples to investigate (i) the environmental distribution, (ii) the ecological niche of A. terreus in Tyrol, (iii) the genetic relatedness of environmental and clinical isolates and the correlation between those two groups of isolates, and (iv) the antifungal susceptibility patterns. A. terreus was present in 5.4% of 3845 environmental samples, with a significantly higher frequency during winter (6.8%) than summer (3.9%). An increased A. terreus abundance in Tyrol’s Eastern part was detected which is in agreement with the proof of clinical cases. In total, 92% of environmental and 98% of clinical A. terreus isolates were amphotericin B resistant; 22.6% and 9.8% were resistant against posaconazole. Overall, 3.9% of clinical isolates were resistant against voriconazole. Short tandem repeat analysis identified three major genotypes persisting in Tyrol. Soil from agricultural cornfields seems to be an important source; the environmental frequency of A. terreus correlates with the high incidence of A. terreus infections in certain geographical areas. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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12 pages, 616 KiB  
Article
Phylogenetic Identification, Diversity, and Richness of Aspergillus from Homes in Havana, Cuba
by Kenia C. Sánchez Espinosa, Michel Almaguer Chávez, Esperanza Duarte-Escalante, Teresa Irene Rojas Flores, María Guadalupe Frías-De-León and María del Rocío Reyes-Montes
Microorganisms 2021, 9(1), 115; https://doi.org/10.3390/microorganisms9010115 - 6 Jan 2021
Cited by 6 | Viewed by 2287
Abstract
Aspergillus is one of the most common fungal genera found indoors; it is important because it can cause a wide range of diseases in humans. Aspergillus species identification is based on a combination of morphological, physiological, and molecular methods. However, molecular methodologies have [...] Read more.
Aspergillus is one of the most common fungal genera found indoors; it is important because it can cause a wide range of diseases in humans. Aspergillus species identification is based on a combination of morphological, physiological, and molecular methods. However, molecular methodologies have rarely been used for the identification of environmental isolates of Aspergillus in Cuba. Therefore, the objective of this work was to identify the species of the genus Aspergillus obtained from houses in Havana, Cuba, through the construction of phylogeny from a partial sequence of the benA gene region, and to analyze the diversity and richness of Aspergillus in the studied municipalities. Isolates of Aspergillus spp. included in this study presented the typical macro- and micromorphology described for the genus. According to this polyphasic characterization, A. niger, A. flavus, A. welwitschiae, A. heteromorphus, A. sydowii, A. tamarii, A. fumigatus, A. clavatus, and A. tubingensis were the most abundant species. Most of the identified species constitute new records for outdoor and indoor environments in Cuba and contribute to the knowledge of fungal biodiversity in the country. These results constitute an alert for the health authorities of the country, since prolonged exposure of the inhabitants to Aspergillus spores can cause severe persistent asthma, among other diseases. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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10 pages, 548 KiB  
Article
Azole-Resistant Aspergillus fumigatus Harboring the TR34/L98H Mutation: First Report in Portugal in Environmental Samples
by Paulo Gonçalves, Aryse Melo, Marta Dias, Beatriz Almeida, Liliana Aranha Caetano, Cristina Veríssimo, Carla Viegas and Raquel Sabino
Microorganisms 2021, 9(1), 57; https://doi.org/10.3390/microorganisms9010057 - 28 Dec 2020
Cited by 21 | Viewed by 3842
Abstract
Introduction: The frequency in detection of azole-resistant Aspergillus fumigatus isolates has increased since 2010. In Portugal, the section Fumigati is one of the most frequent, and resistant strains to have been found in clinical and environmental contexts. Although several cryptic species within the [...] Read more.
Introduction: The frequency in detection of azole-resistant Aspergillus fumigatus isolates has increased since 2010. In Portugal, the section Fumigati is one of the most frequent, and resistant strains to have been found in clinical and environmental contexts. Although several cryptic species within the Fumigati section show intrinsic resistance to azoles, one factor driving (acquired) resistance is selective pressure deriving from the extensive use of azoles. This is particularly problematic in occupational environments where high fungal loads are expected, and where there is an increased risk of human exposure and infection, with impact on treatment success and disease outcome. The mechanisms of resistance are diverse, but mainly associated with mutations in the cyp51A gene. Despite TR34/L98H being the most frequent mutation described, it has only been detected in clinical specimens in Portugal. Methods: We analyzed 99 A. fumigatus isolates from indoor environments (healthcare facilities, spas, one dairy and one waste sorting unit) collected from January 2018 to February 2019 in different regions of Portugal. Isolates were screened for resistance to itraconazole, voriconazole and posaconazole by culture, and resistance was confirmed by broth microdilution. Sequencing of the cyp51A gene and its promoter was performed to detect mutations associated with resistance. Results: Overall, 8.1% of isolates were able to grow in the presence of at least one azole, and 3% (isolated from the air in a dairy and from filtering respiratory protective devices in a waste sorting industry) were pan-azole-resistant, bearing the TR34/L98H mutation. Conclusion: For the first time in Portugal, we report environmental isolates bearing the TR34/L98H mutation, isolated from occupational environments. Environmental surveillance of the emergence of azole-resistant A. fumigatus sensu stricto strains is needed, to ensure proper and timely implementation of control policies that may have a positive impact on public and occupational health. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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14 pages, 665 KiB  
Article
Establishment of a New PNA-FISH Method for Aspergillus fumigatus Identification: First Insights for Future Use in Pulmonary Samples
by Laura Cerqueira, Sara Moura, Carina Almeida, Maria João Vieira and Nuno Filipe Azevedo
Microorganisms 2020, 8(12), 1950; https://doi.org/10.3390/microorganisms8121950 - 9 Dec 2020
Cited by 6 | Viewed by 1960
Abstract
Aspergillus fumigatus is the main causative agent of Invasive Aspergillosis. This mold produces conidia that when inhaled by immunocompromized hosts can be deposited in the lungs and germinate, triggering disease. In this paper, the development of a method using peptide nucleic acid-fluorescence in [...] Read more.
Aspergillus fumigatus is the main causative agent of Invasive Aspergillosis. This mold produces conidia that when inhaled by immunocompromized hosts can be deposited in the lungs and germinate, triggering disease. In this paper, the development of a method using peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) is described. The PNA-FISH probe was tested in several strains and a specificity and sensitivity of 100% was obtained. Detection of A. fumigatussensu stricto was then achieved in artificial sputum medium (ASM) pre-inoculated with 1 × 102 conidia·mL−1–1 × 103 conidia·mL−1, after a germination step of 24 h. The PNA-FISH method was evaluated in 24 clinical samples (10 sputum, 8 bronchoalveolar lavage (BAL), and 6 bronchial lavage (BL)) that were inoculated with 1 × 104 conidia·mL−1 in sputum; 1 × 103 conidia·mL−1 in BL and BAL, for 24 h. Despite a specificity of 100%, the sensitivity was 79%. This relatively low sensitivity can be explained by the fact that hyphae can yield “fungal ball“ clusters, hindering pipetting procedures and subsequent detection, leading to false negative results. Nonetheless, this study showed the potential of the PNA-FISH method for A. fumigatussensu stricto detection since it takes only 1 h 30 m to perform the procedure with a pre-enrichment step of 6 h (pure cultures) and 24 h (clinical samples), and might provide a suitable alternative to the existing methods for studies in pure cultures and in clinical settings. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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19 pages, 1762 KiB  
Article
Comparative Genome Sequence Analyses of Geographic Samples of Aspergillus fumigatus—Relevance for Amphotericin B Resistance
by Yuying Fan, Yue Wang and Jianping Xu
Microorganisms 2020, 8(11), 1673; https://doi.org/10.3390/microorganisms8111673 - 28 Oct 2020
Cited by 11 | Viewed by 2150
Abstract
Amphotericin B (AMB) is a major fungicidal polyene agent that has a broad spectrum of action against invasive fungal infections. AMB is typically used as the last-line drug against serious and life-threatening infections when other drugs have failed to eliminate the fungal pathogens. [...] Read more.
Amphotericin B (AMB) is a major fungicidal polyene agent that has a broad spectrum of action against invasive fungal infections. AMB is typically used as the last-line drug against serious and life-threatening infections when other drugs have failed to eliminate the fungal pathogens. Recently, AMB resistance in Aspergillus fumigatus has become more evident. For example, a high rate of AMB resistance (96%) was noted in the A. fumigatus population in Hamilton, Ontario, Canada. AMB-resistant strains have also been found in other countries. However, the mechanism of AMB resistance remains largely unknown. Here, we investigated the potential genes and mutations associated with AMB resistance using whole-genome sequences and examined AMB resistance distribution among genetic populations. A total of 196 whole-genome sequences representing strains from 11 countries were examined. Analyses of single nucleotide polymorphisms (SNPs) at the whole-genome level revealed that these strains belonged to three divergent genetic clusters, with the majority (90%) of AMB resistant strains located in one of the three clusters, Cluster 2. Our analyses identified over 60 SNPs significantly associated with AMB resistance. Together, these SNPs represent promising candidates from which to investigate the putative molecular mechanisms of AMB resistance and for their potential use in developing rapid diagnostic markers for clinical screening of AMB resistance in A. fumigatus. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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11 pages, 762 KiB  
Article
Colistin and Isavuconazole Interact Synergistically In Vitro against Aspergillus nidulans and Aspergillus niger
by Patrick Schwarz, Elie Djenontin and Eric Dannaoui
Microorganisms 2020, 8(9), 1447; https://doi.org/10.3390/microorganisms8091447 - 21 Sep 2020
Cited by 8 | Viewed by 2076
Abstract
The in vitro interactions of isavuconazole in combination with colistin were evaluated against 55 clinical Aspergillus species isolates belonging to the five most important species (Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus) responsible [...] Read more.
The in vitro interactions of isavuconazole in combination with colistin were evaluated against 55 clinical Aspergillus species isolates belonging to the five most important species (Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus) responsible for human aspergillosis by a microdilution checkerboard technique based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference method for antifungal susceptibility testing. Selected isolates (A. nidulans, n = 10; A. niger, n = 15) were additionally evaluated by an agar diffusion assay using isavuconazole gradient concentration strips with or without colistin incorporated Roswell Parc Memorial Institute (RPMI) agar. Interpretation of the checkerboard results was done by the fractional inhibitory concentration index. Using the checkerboard method, combination isavuconazole–colistin was synergistic for 100% of the 15 A. nidulans isolates and for 60% of the 20 A. niger isolates. No interactions were found for any of the other isolates. By agar diffusion assay, minimal inhibitory concentrations (MICs) in combination decreased compared to isavuconazole alone for 92% of the isolates. No interactions were found for any A. nidulans isolates, but synergy was observed for 40% of the A. niger isolates. A poor essential agreement of EUCAST and gradient concentration strip MICs at ± 2 log2 dilutions with 0% was obtained. Antagonistic interactions were never observed regardless of the technique used. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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13 pages, 3895 KiB  
Article
Genome Wide Analysis Reveals the Role of VadA in Stress Response, Germination, and Sterigmatocystin Production in Aspergillus nidulans Conidia
by Ye-Eun Son and Hee-Soo Park
Microorganisms 2020, 8(9), 1319; https://doi.org/10.3390/microorganisms8091319 - 30 Aug 2020
Cited by 11 | Viewed by 2420
Abstract
In the Aspergillus species, conidia are asexual spores that are infectious particles responsible for propagation. Conidia contain various mycotoxins that can have detrimental effects in humans. Previous study demonstrated that VadA is required for fungal development and spore viability in the model fungus [...] Read more.
In the Aspergillus species, conidia are asexual spores that are infectious particles responsible for propagation. Conidia contain various mycotoxins that can have detrimental effects in humans. Previous study demonstrated that VadA is required for fungal development and spore viability in the model fungus Aspergillus nidulans. In the present study, vadA transcriptomic analysis revealed that VadA affects the mRNA expression of a variety of genes in A. nidulans conidia. The genes that were primarily affected in conidia were associated with trehalose biosynthesis, cell-wall integrity, stress response, and secondary metabolism. Genetic changes caused by deletion of vadA were related to phenotypes of the vadA deletion mutant conidia. The deletion of vadA resulted in increased conidial sensitivity against ultraviolet stress and induced germ tube formation in the presence and absence of glucose. In addition, most genes in the secondary metabolism gene clusters of sterigmatocystin, asperfuranone, monodictyphenone, and asperthecin were upregulated in the mutant conidia with vadA deletion. The deletion of vadA led to an increase in the amount of sterigmatocystin in the conidia, suggesting that VadA is essential for the repression of sterigmatocystin production in conidia. These results suggest that VadA coordinates conidia maturation, stress response, and secondary metabolism in A. nidulans conidia. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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Review

Jump to: Editorial, Research

14 pages, 718 KiB  
Review
Bacterial Interactions with Aspergillus fumigatus in the Immunocompromised Lung
by Anatte Margalit, James C. Carolan and Kevin Kavanagh
Microorganisms 2021, 9(2), 435; https://doi.org/10.3390/microorganisms9020435 - 19 Feb 2021
Cited by 9 | Viewed by 3760
Abstract
The immunocompromised airways are susceptible to infections caused by a range of pathogens which increases the opportunity for polymicrobial interactions to occur. Pseudomonas aeruginosa and Staphylococcus aureus are the predominant causes of pulmonary infection for individuals with respiratory disorders such as cystic fibrosis [...] Read more.
The immunocompromised airways are susceptible to infections caused by a range of pathogens which increases the opportunity for polymicrobial interactions to occur. Pseudomonas aeruginosa and Staphylococcus aureus are the predominant causes of pulmonary infection for individuals with respiratory disorders such as cystic fibrosis (CF). The spore-forming fungus Aspergillus fumigatus, is most frequently isolated with P. aeruginosa, and co-infection results in poor outcomes for patients. It is therefore clinically important to understand how these pathogens interact with each other and how such interactions may contribute to disease progression so that appropriate therapeutic strategies may be developed. Despite its persistence in the airways throughout the life of a patient, A. fumigatus rarely becomes the dominant pathogen. In vitro interaction studies have revealed remarkable insights into the molecular mechanisms that drive agonistic and antagonistic interactions that occur between A. fumigatus and pulmonary bacterial pathogens such as P. aeruginosa. Crucially, these studies demonstrate that although bacteria may predominate in a competitive environment, A. fumigatus has the capacity to persist and contribute to disease. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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Graphical abstract

23 pages, 3060 KiB  
Review
Aspergillosis, Avian Species and the One Health Perspective: The Possible Importance of Birds in Azole Resistance
by Aryse Martins Melo, David A. Stevens, Lisa A. Tell, Cristina Veríssimo, Raquel Sabino and Melissa Orzechowski Xavier
Microorganisms 2020, 8(12), 2037; https://doi.org/10.3390/microorganisms8122037 - 19 Dec 2020
Cited by 29 | Viewed by 6764
Abstract
The One Health context considers health based on three pillars: humans, animals, and environment. This approach is a strong ally in the surveillance of infectious diseases and in the development of prevention strategies. Aspergillus spp. are fungi that fit substantially in this context, [...] Read more.
The One Health context considers health based on three pillars: humans, animals, and environment. This approach is a strong ally in the surveillance of infectious diseases and in the development of prevention strategies. Aspergillus spp. are fungi that fit substantially in this context, in view of their ubiquity, as well as their importance as plant pathogens, and potentially fatal pathogens for, particularly, humans and avian species. In addition, the emergence of azole resistance, mainly in Aspergillus fumigatus sensu stricto, and the proven role of fungicides widely used on crops, reinforces the need for a multidisciplinary approach to this problem. Avian species are involved in short and long distance travel between different types of landscapes, such as agricultural fields, natural environments and urban environments. Thus, birds can play an important role in the dispersion of Aspergillus, and of special concern, azole-resistant strains. In addition, some bird species are particularly susceptible to aspergillosis. Therefore, avian aspergillosis could be considered as an environmental health indicator. In this review, aspergillosis in humans and birds will be discussed, with focus on the presence of Aspergillus in the environment. We will relate these issues with the emergence of azole resistance on Aspergillus. These topics will be therefore considered and reviewed from the “One Health” perspective. Full article
(This article belongs to the Special Issue Aspergillus and Health 1.0)
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