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Pathogens
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Aspergillosis
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Aspergillosis

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Fungal Pathogens".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 29372

Special Issue Editor

Dr. Sara Gago

E-Mail Website
Guest Editor
Division of Infection, Immunity & Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, UK
Interests: aspergillosis; host–pathogen interaction; fungal disease mechanisms; diagnosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Fungal infections are a growing health concern. Every year, more die from fungal diseases than either tuberculosis or malaria. Aspergillus fumigatus is an environmental opportunistic fungal pathogen responsible for a disease, aspergillosis, which globally affects more than 10 million people. Aspergillus disease mainly affects people with an impaired lung defences arising from severe immunosuppression or an underlying chronic respiratory condition. Studies in the past few years have identified new potential host and pathogen factors involved in pathogenicity by using multi-omics approaches. However, the pathogenesis of the disease is still poorly understood. Additionally, the rates of antifungal resistance are increasing year by year and identification of new host and pathogen factors is critical for the development of new diagnostics and treatments. For this Special Issue of Pathogens, we invite you to submit research articles, review articles, short notes as well as communications related to the epidemiology of aspergillosis, Aspergillus pathogenicity factors, fungus – host interactions and host response against Aspergillus. We look forward to your contribution.

Dr. Sara Gago
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.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 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

  • Aspergillus
  • Aspergillosis
  • Epidemiology
  • Diagnostics
  • Disease Modelling
  • Antifungal therapy
  • Host response
  • Genetics
  • Pathogenicity factors

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Published Papers (7 papers)

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Research

Jump to: Review

18 pages, 1497 KiB  
Article
Assessing Differences between Clinical Isolates of Aspergillus fumigatus from Cases of Proven Invasive Aspergillosis and Colonizing Isolates with Respect to Phenotype (Virulence in Tenebrio molitor Larvae) and Genotype
by Sam El-Kamand, Martina Steiner, Carl Ramirez, Catriona Halliday, Sharon C.-A. Chen, Alexie Papanicolaou and Charles Oliver Morton
Pathogens 2022, 11(4), 428; https://doi.org/10.3390/pathogens11040428 - 31 Mar 2022
Cited by 2 | Viewed by 3088
Abstract
The fungus Aspergillus fumigatus, the cause of invasive aspergillosis (IA), is a serious risk to transplant patients and those with respiratory diseases. Host immune suppression is considered the most important factor for the development of IA. Less is known about the importance [...] Read more.
The fungus Aspergillus fumigatus, the cause of invasive aspergillosis (IA), is a serious risk to transplant patients and those with respiratory diseases. Host immune suppression is considered the most important factor for the development of IA. Less is known about the importance of fungal virulence in the development of IA including the significance of variation between isolates. In this study, isolates of A. fumigatus from cases diagnosed as having proven IA or colonisation (no evidence of IA) were compared in assays to measure isolate virulence. These assays included the measurement of radial growth and protease production on agar, sensitivity to UV light and oxidative stressors, and virulence in Tenebrio molitor (mealworm) larvae. These assays did not reveal obvious differences in virulence between the two groups of isolates; this provided the impetus to conduct genomic analysis. Whole genome sequencing and analysis did not allow grouping into coloniser or IA isolates. However, focused analysis of single nucleotide polymorphisms revealed variation in three putative genes: AFUA_5G09420 (ccg-8), AFUA_4G00330, and AFUA_4G00350. These are known to be responsive to azole exposure, and ccg-8 deletion leads to azole hypersensitivity in other fungi. A. fumigatus virulence is challenging, but the findings of this study indicate that further research into the response to oxidative stress and azole exposure are required to understand the development of IA. Full article
(This article belongs to the Special Issue Aspergillosis)
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12 pages, 989 KiB  
Article
Incidence and Risk Factors of COVID-19-Associated Pulmonary Aspergillosis in Intensive Care Unit—A Monocentric Retrospective Observational Study
by Emilien Gregoire, Benoit François Pirotte, Filip Moerman, Antoine Altdorfer, Laura Gaspard, Eric Firre, Martial Moonen, Vincent Fraipont, Marie Ernst and Gilles Darcis
Pathogens 2021, 10(11), 1370; https://doi.org/10.3390/pathogens10111370 - 22 Oct 2021
Cited by 12 | Viewed by 2232
Abstract
Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is an increasingly recognized complication of COVID-19 and is associated with significant over-mortality. We performed a retrospective monocentric study in patients admitted to the intensive care unit (ICU) for respiratory insufficiency due to COVID-19 from March [...] Read more.
Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is an increasingly recognized complication of COVID-19 and is associated with significant over-mortality. We performed a retrospective monocentric study in patients admitted to the intensive care unit (ICU) for respiratory insufficiency due to COVID-19 from March to December 2020, in order to evaluate the incidence of CAPA and the associated risk factors. We also analysed the diagnostic approach used in our medical centre for CAPA diagnosis. We defined CAPA using recently proposed consensus definitions based on clinical, radiological and microbiological criteria. Probable cases of CAPA occurred in 9 out of 141 patients included in the analysis (6.4%). All cases were diagnosed during the second wave of the pandemic. We observed a significantly higher realization rate of bronchoalveolar lavage (BAL) (51.1% vs. 28.6%, p = 0.01) and Aspergillus testing (through galactomannan, culture, PCR) on BAL samples during the second wave (p < 0.0001). The testing for Aspergillus in patients meeting the clinical and radiological criteria of CAPA increased between the two waves (p < 0.0001). In conclusion, we reported a low but likely underestimated incidence of CAPA in our population. A greater awareness and more systematic testing for Aspergillus are necessary to assess the real incidence and characteristics of CAPA. Full article
(This article belongs to the Special Issue Aspergillosis)
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10 pages, 1640 KiB  
Article
Transcription Factor HSF1 Suppresses the Expression of Surfactant Protein D in Cells Infected with Aspergillus fumigatus
by Sung-Su Kim and Kwang-Soo Shin
Pathogens 2021, 10(6), 709; https://doi.org/10.3390/pathogens10060709 - 6 Jun 2021
Cited by 2 | Viewed by 2286
Abstract
Aspergillosis is a life-threatening disease in patients with compromised immune systems. The process of fungal invasion is an important step during host cell infection. We investigated the transcription factor and promoter region of SFTPD, which is activated during the infection process in conidia-treated [...] Read more.
Aspergillosis is a life-threatening disease in patients with compromised immune systems. The process of fungal invasion is an important step during host cell infection. We investigated the transcription factor and promoter region of SFTPD, which is activated during the infection process in conidia-treated cells. To investigate the promoter activity of SFTPD in fungal-infected cells, we cloned various lengths of the promoter region (−1000 to +1) of SFTPD and examined its activity in A549 cells treated with Aspergillus fumigatus conidia. We determined the location within the promoter region of SFTPD that exhibits a response to conidia infection. AliBaba 2.1 software was used to predict the transcription factor involved as well as the binding sites in the SFTPD promoter region. The results of a decoy assay show that the HSF1 transcription factor is sufficient to decrease the SFTPD expression. Using chromatin immunoprecipitation, we confirmed that HSF1 directly binds to the selected sequence, which is located in the response region (−142 to −134 bp). These findings suggest that inhibiting the binding of HSF1 to the promoter region of SFTPD is an important step to prevent conidia infection. Full article
(This article belongs to the Special Issue Aspergillosis)
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34 pages, 4576 KiB  
Article
Genome-Wide Association Analysis for Triazole Resistance in Aspergillus fumigatus
by Yuying Fan, Yue Wang, Gregory A. Korfanty, Meagan Archer and Jianping Xu
Pathogens 2021, 10(6), 701; https://doi.org/10.3390/pathogens10060701 - 4 Jun 2021
Cited by 17 | Viewed by 3736
Abstract
Aspergillus fumigatus is a ubiquitous fungus and the main agent of aspergillosis, a common fungal infection in the immunocompromised population. Triazoles such as itraconazole and voriconazole are the common first-line drugs for treating aspergillosis. However, triazole resistance in A. fumigatus has been reported [...] Read more.
Aspergillus fumigatus is a ubiquitous fungus and the main agent of aspergillosis, a common fungal infection in the immunocompromised population. Triazoles such as itraconazole and voriconazole are the common first-line drugs for treating aspergillosis. However, triazole resistance in A. fumigatus has been reported in an increasing number of countries. While most studies of triazole resistance have focused on mutations in the triazole target gene cyp51A, >70% of triazole-resistant strains in certain populations showed no mutations in cyp51A. To identify potential non-cyp51A mutations associated with triazole resistance in A. fumigatus, we analyzed the whole genome sequences and triazole susceptibilities of 195 strains from 12 countries. These strains belonged to three distinct clades. Our genome-wide association study (GWAS) identified a total of six missense mutations significantly associated with itraconazole resistance and 18 missense mutations with voriconazole resistance. In addition, to investigate itraconazole and pan-azole resistance, Fisher’s exact tests revealed 26 additional missense variants tightly linked to the top 20 SNPs obtained by GWAS, of which two were consistently associated with triazole resistance. The large number of novel mutations related to triazole resistance should help further investigations into their molecular mechanisms, their clinical importance, and the development of a comprehensive molecular diagnosis toolbox for triazole resistance in A. fumigatus. Full article
(This article belongs to the Special Issue Aspergillosis)
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Review

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17 pages, 1302 KiB  
Review
Aspergillus Genus and Its Various Human Superficial and Cutaneous Features
by Yassine Merad, Hichem Derrar, Zoubir Belmokhtar and Malika Belkacemi
Pathogens 2021, 10(6), 643; https://doi.org/10.3390/pathogens10060643 - 23 May 2021
Cited by 21 | Viewed by 6573
Abstract
Superficial and cutaneous aspergillosis is a rare fungal disease that is restricted to the outer layers of the skin, nails, and the outer auditory canal, infrequently invading the deeper tissue and viscera, particularly in immunocompromised patients. These mycoses are acquired through two main [...] Read more.
Superficial and cutaneous aspergillosis is a rare fungal disease that is restricted to the outer layers of the skin, nails, and the outer auditory canal, infrequently invading the deeper tissue and viscera, particularly in immunocompromised patients. These mycoses are acquired through two main routes: direct traumatic inoculation or inhalation of airborne fungal spores into paranasal sinuses and lungs. Lesions are classified into three categories: otomycosis, onychomycosis, and cutaneous aspergillosis. Superficial and cutaneous aspergillosis occurs less frequently and therefore remains poorly characterized; it usually involves sites of superficial trauma—namely, at or near intravenous entry catheter site, at the point of traumatic inoculation (orthopaedic inoculation, ear-self-cleaning, schizophrenic ear self-injuries), at surgery incision, and at the site of contact with occlusive dressings, especially in burn patients. Onychomycosis and otomycosis are more seen in immunocompetent patients, while cutaneous aspergillosis is widely described among the immunocompromised individuals. This paper is a review of related literature. Full article
(This article belongs to the Special Issue Aspergillosis)
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13 pages, 251 KiB  
Review
Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches
by Claudia Lattanzi, Giulia Messina, Valentina Fainardi, Maria Candida Tripodi, Giovanna Pisi and Susanna Esposito
Pathogens 2020, 9(9), 716; https://doi.org/10.3390/pathogens9090716 - 31 Aug 2020
Cited by 13 | Viewed by 3797
Abstract
Cystic fibrosis (CF), the most common autosomal-recessive genetic disease in the Caucasian population, is characterized by frequent respiratory infections and progressive lung disease. Fungal species are commonly found in patients with CF, and among them, Aspergillus fumigatus is the most frequently isolated. While [...] Read more.
Cystic fibrosis (CF), the most common autosomal-recessive genetic disease in the Caucasian population, is characterized by frequent respiratory infections and progressive lung disease. Fungal species are commonly found in patients with CF, and among them, Aspergillus fumigatus is the most frequently isolated. While bacteria, particularly Pseudomonas aeruginosa, have a well-established negative effect on CF lung disease, the impact of fungal infections remains unclear. In patients with CF, inhalation of Aspergillus conidia can cause allergic bronchopulmonary aspergillosis (ABPA), a Th2-mediated lung disease that can contribute to disease progression. Clinical features, diagnostic criteria and treatment of ABPA are still a matter of debate. Given the consequences of a late ABPA diagnosis or the risk of ABPA overdiagnosis, it is imperative that the diagnostic criteria guidelines are reviewed and standardized. Along with traditional criteria, radiological features are emerging as tools for further classification as well as novel immunological tests. Corticosteroids, itraconazole and voriconazole continue to be the bedrock of ABPA therapy, but other molecules, such as posaconazole, vitamin D, recombinant INF-γ and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators, have been showing positive results. However, few studies have been conducted recruiting CF patients, and more research is needed to improve the prevention and the classification of clinical manifestations as well as to personalize treatment. Early recognition and early treatment of fungal infections may be fundamental to prevent progression of CF disease. The aim of this narrative review is to give an update on ABPA in children with CF. Full article
(This article belongs to the Special Issue Aspergillosis)
19 pages, 634 KiB  
Review
Factoring in the Complexity of the Cystic Fibrosis Lung to Understand Aspergillus fumigatus and Pseudomonas aeruginosa Interactions
by Emily Beswick, Jorge Amich and Sara Gago
Pathogens 2020, 9(8), 639; https://doi.org/10.3390/pathogens9080639 - 6 Aug 2020
Cited by 15 | Viewed by 6217
Abstract
Pseudomonas aeruginosa has long been established as the most prevalent respiratory pathogen in Cystic Fibrosis (CF) patients, with opportunistic infection causing profound morbidity and mortality. Recently, Aspergillus fumigatus has also been recognised as a key contributor to CF lung deterioration, being consistently associated [...] Read more.
Pseudomonas aeruginosa has long been established as the most prevalent respiratory pathogen in Cystic Fibrosis (CF) patients, with opportunistic infection causing profound morbidity and mortality. Recently, Aspergillus fumigatus has also been recognised as a key contributor to CF lung deterioration, being consistently associated with decreased lung function and worsened prognosis in these patients. As clinical evidence for the common occurrence of combined infection with these two pathogens increases, research into the mechanism and consequences of their interaction is becoming more relevant. Clinical evidence suggests a synergistic effect of combined infection, which translates into a poorer prognosis for the patients. In vitro results from the laboratory have identified a variety of possible synergistic and antagonistic interactions between A. fumigatus and P. aeruginosa. Here, we present a comprehensive overview of the complex environment of the CF lung and discuss how it needs to be considered to determine the exact molecular interactions that A. fumigatus and P. aeruginosa undergo during combined infection and their effects on the host. Full article
(This article belongs to the Special Issue Aspergillosis)
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