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Aspergillus Infections—Virulence and Host Response
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Aspergillus Infections—Virulence and Host Response

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 10629

Special Issue Editors

Prof. Dr. Frank Ebel

E-Mail Website
Guest Editor
Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-University of Munich, Munich, Germany
Interests: mycology; microbiology; immunology
Special Issues, Collections and Topics in MDPI journals
Sebastian Schrüfer

E-Mail Website
Guest Editor Assistant
Institute for Infectious Diseases and Zoonoses, LMU Munich, Germany
Interests: signaling pathways; host-pathogen interactions; closure of septal pores; antibodies; eosinophils

Special Issue Information

Dear Colleagues,

Aspergillus fumigatus and other pathogenic species of the genus Aspergillus are the causative agents of a variety of infections that can affect humans as well as animals. The spectrum of diseases ranges from mild allergic reactions and locally restricted infections, such as ABPA and aspergillomas, to severe and life-threatening systemic mycoses. In recent decades, cases of systemic aspergillosis have mainly affected severely immunocompromised patients, e.g.,  after stem cell transplantation. However, the recent pandemic has led to an onset of COVID-19-associated pulmonary aspergillosis (CAPA), which in turn has sparked increased interest in influenza-associated cases of aspergillosis.

The focus of this Special Issue will be on studies around the fungal and host side of aspergillosis. Virulence traits include any aspects of fungal biology that contribute to its pathogenic potential or stress resilience. Depending on the type of disease, host responses differ depending on the interplay between host and pathogen. The resulting immune response can either solve an infection or, in other cases, even be detrimental and result in severe collateral damage.

Prof. Dr. Frank Ebel
Guest Editor
Sebastian Schrüfer
Guest Editor Assistant

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

  • invasive aspergillosis
  • ABPA
  • CAPA
  • virulence factor
  • stress resistance
  • immune response

Published Papers (5 papers)

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Research

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15 pages, 6198 KiB  
Article
Characterization of Lung Inflammatory Response to Aspergillus fumigatus Spores
by Alexandra Bouyssi, Tanguy Déméautis, Alexis Trecourt, Marie Delles, Fany Agostini, Guillaume Monneret, Olivier Glehen, Martine Wallon, Florence Persat, Gilles Devouassoux, Abderrazzak Bentaher and Jean Menotti
J. Fungi 2023, 9(6), 682; https://doi.org/10.3390/jof9060682 - 17 Jun 2023
Cited by 2 | Viewed by 1375
Abstract
The airway exposure to Aspergillus fumigatus spores (AFsp) is associated with an inflammatory response, potentially leading to allergic and/or chronic pulmonary aspergillosis. The aim of our study is to better understand the host response, first in vitro, then in vivo, following the chronic [...] Read more.
The airway exposure to Aspergillus fumigatus spores (AFsp) is associated with an inflammatory response, potentially leading to allergic and/or chronic pulmonary aspergillosis. The aim of our study is to better understand the host response, first in vitro, then in vivo, following the chronic exposure of mice to AFsp. We investigated the inflammatory response to AFsp in cell mono- and co-culture systems with murine macrophages and alveolar epithelial cells. The mice were subjected to two intranasal instillations using 105 AFsp. Their lungs were processed for inflammatory and histopathological analyses. In cell culture, the gene expressions significantly increased for TNF-α, CXCL-1, CXCL-2, IL-1β, IL-1α and GM-CSF in macrophages, with these increases being limited for TNF-α, CXCL-1 and IL-1α in epithelial cells. In co-culture, increases in the TNF-α, CXCL-2 and CXCL-1 gene expressions were observed to be associated with increased protein levels. The in vivo lung histological analyses of mice challenged by AFsp showed cellular infiltrates in the peribronchial and/or alveolar spaces. A Bio-Plex approach on the bronchoalveolar lavage revealed significant increases in the protein secretion of selected mediators of the challenged mice compared to the unchallenged mice. In conclusion, the exposure to AFsp resulted in a marked inflammatory response of macrophages and epithelial cells. These inflammatory findings were confirmed in mouse models associated with lung histologic changes. Full article
(This article belongs to the Special Issue Aspergillus Infections—Virulence and Host Response)
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19 pages, 3490 KiB  
Article
Survival Factor A (SvfA) Contributes to Aspergillus nidulans Pathogenicity
by Joo-Yeon Lim, Ye-Eun Jung, Hye-Eun Hwang, Cheol-Hee Kim, Nese Basaran-Akgul, Sri Harshini Goli, Steven P. Templeton and Hee-Moon Park
J. Fungi 2023, 9(2), 143; https://doi.org/10.3390/jof9020143 - 21 Jan 2023
Cited by 1 | Viewed by 2099
Abstract
Survival factor A (SvfA) in Aspergillus nidulans plays multiple roles in growth and developmental processes. It is a candidate for a novel VeA-dependent protein involved in sexual development. VeA is a key developmental regulator in Aspergillus species that can interact with other velvet-family proteins [...] Read more.
Survival factor A (SvfA) in Aspergillus nidulans plays multiple roles in growth and developmental processes. It is a candidate for a novel VeA-dependent protein involved in sexual development. VeA is a key developmental regulator in Aspergillus species that can interact with other velvet-family proteins and enter into the nucleus to function as a transcription factor. In yeast and fungi, SvfA-homologous proteins are required for survival under oxidative and cold-stress conditions. To assess the role of SvfA in virulence in A. nidulans, cell wall components, biofilm formation, and protease activity were evaluated in a svfA-gene-deletion or an AfsvfA-overexpressing strain. The svfA-deletion strain showed decreased production of β-1,3-glucan in conidia, a cell wall pathogen-associated molecular pattern, with a decrease in gene expression for chitin synthases and β-1,3-glucan synthase. The ability to form biofilms and produce proteases was reduced in the svfA-deletion strain. We hypothesized that the svfA-deletion strain was less virulent than the wild-type strain; therefore, we performed in vitro phagocytosis assays using alveolar macrophages and analyzed in vivo survival using two vertebrate animal models. While phagocytosis was reduced in mouse alveolar macrophages challenged with conidia from the svfA-deletion strain, the killing rate showed a significant increase with increased extracellular signal-regulated kinase ERK activation. The svfA-deletion conidia infection reduced host mortality in both T-cell-deficient zebrafish and chronic granulomatous disease mouse models. Taken together, these results indicate that SvfA plays a significant role in the pathogenicity of A. nidulans. Full article
(This article belongs to the Special Issue Aspergillus Infections—Virulence and Host Response)
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10 pages, 2428 KiB  
Article
Gut Microbial Disruption in Critically Ill Patients with COVID-19-Associated Pulmonary Aspergillosis
by H. Carlo Maurer, David Schult, Plamena Koyumdzhieva, Sandra Reitmeier, Moritz Middelhoff, Sebastian Rasch, Markus List, Klaus-Peter Janssen, Katja Steiger, Ulrike Protzer, Roland M. Schmid, Klaus Neuhaus, Dirk Haller, Michael Quante and Tobias Lahmer
J. Fungi 2022, 8(12), 1265; https://doi.org/10.3390/jof8121265 - 30 Nov 2022
Viewed by 1781
Abstract
Objectives: COVID-19 disease can be exacerbated by Aspergillus superinfection (CAPA). However, the causes of CAPA are not yet fully understood. Recently, alterations in the gut microbiome have been associated with a more complicated and severe disease course in COVID-19 patients, most likely due [...] Read more.
Objectives: COVID-19 disease can be exacerbated by Aspergillus superinfection (CAPA). However, the causes of CAPA are not yet fully understood. Recently, alterations in the gut microbiome have been associated with a more complicated and severe disease course in COVID-19 patients, most likely due to immunological mechanisms. The aim of this study was to investigate a potential association between severe CAPA and alterations in the gut and bronchial microbial composition. Methods: We performed 16S rRNA gene amplicon sequencing of stool and bronchial samples from a total of 16 COVID-19 patients with CAPA and 26 patients without CAPA. All patients were admitted to the intensive care unit. Results were carefully tested for potentially confounding influences on the microbiome during hospitalization. Results: We found that late in COVID-19 disease, CAPA patients exhibited a trend towards reduced gut microbial diversity. Furthermore, late-stage patients with CAPA superinfection exhibited an increased abundance of Staphylococcus epidermidis in the gut which was not found in late non-CAPA cases or early in the disease. The analysis of bronchial samples did not yield significant results. Conclusions: This is the first study showing that alterations in the gut microbiome accompany severe CAPA and possibly influence the host’s immunological response. In particular, an increase in Staphylococcus epidermidis in the intestine could be of importance. Full article
(This article belongs to the Special Issue Aspergillus Infections—Virulence and Host Response)
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Review

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42 pages, 2539 KiB  
Review
Chitin Biosynthesis in Aspergillus Species
by Veronica S. Brauer, André M. Pessoni, Mateus S. Freitas, Marinaldo P. Cavalcanti-Neto, Laure N. A. Ries and Fausto Almeida
J. Fungi 2023, 9(1), 89; https://doi.org/10.3390/jof9010089 - 06 Jan 2023
Cited by 8 | Viewed by 3312
Abstract
The fungal cell wall (FCW) is a dynamic structure responsible for the maintenance of cellular homeostasis, and is essential for modulating the interaction of the fungus with its environment. It is composed of proteins, lipids, pigments and polysaccharides, including chitin. Chitin synthesis is [...] Read more.
The fungal cell wall (FCW) is a dynamic structure responsible for the maintenance of cellular homeostasis, and is essential for modulating the interaction of the fungus with its environment. It is composed of proteins, lipids, pigments and polysaccharides, including chitin. Chitin synthesis is catalyzed by chitin synthases (CS), and up to eight CS-encoding genes can be found in Aspergillus species. This review discusses in detail the chitin synthesis and regulation in Aspergillus species, and how manipulation of chitin synthesis pathways can modulate fungal growth, enzyme production, virulence and susceptibility to antifungal agents. More specifically, the metabolic steps involved in chitin biosynthesis are described with an emphasis on how the initiation of chitin biosynthesis remains unknown. A description of the classification, localization and transport of CS was also made. Chitin biosynthesis is shown to underlie a complex regulatory network, with extensive cross-talks existing between the different signaling pathways. Furthermore, pathways and recently identified regulators of chitin biosynthesis during the caspofungin paradoxical effect (CPE) are described. The effect of a chitin on the mammalian immune system is also discussed. Lastly, interference with chitin biosynthesis may also be beneficial for biotechnological applications. Even after more than 30 years of research, chitin biosynthesis remains a topic of current interest in mycology. Full article
(This article belongs to the Special Issue Aspergillus Infections—Virulence and Host Response)
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Other

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7 pages, 407 KiB  
Brief Report
Long-Term Follow-Up of Patients Diagnosed with COVID-19-Associated Pulmonary Aspergillosis (CAPA)
by María Ruiz-Ruigómez, Mario Fernández-Ruiz, Ana Pérez-Ayala and José María Aguado
J. Fungi 2022, 8(8), 840; https://doi.org/10.3390/jof8080840 - 11 Aug 2022
Cited by 2 | Viewed by 1328
Abstract
COVID-19-associated pulmonary aspergillosis (CAPA) have been documented during the COVID-19 pandemic. The vast majority of these patients do not meet the classic EORTC/MSGERC criteria for invasive pulmonary aspergillosis. The question arises as to whether there may have been an over-diagnosis of this disease. [...] Read more.
COVID-19-associated pulmonary aspergillosis (CAPA) have been documented during the COVID-19 pandemic. The vast majority of these patients do not meet the classic EORTC/MSGERC criteria for invasive pulmonary aspergillosis. The question arises as to whether there may have been an over-diagnosis of this disease. Here we review our experience and analyze the evolution of 27 patients who were diagnosed with CAPA during hospital admission. Surviving patients were followed-up for a mean time of 15 months (SD 3.78) by a group of experts and clinical records of diseased patients were reviewed. After expert evaluation and follow-up, 10 patients were finally assumed as CAPA according to expert opinion. These cases represent 40% of the initially CAPA assumed cases. Our data suggest the need to reconsider actual diagnosis criteria for CAPA what could drive to better identification of these patients. Full article
(This article belongs to the Special Issue Aspergillus Infections—Virulence and Host Response)
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