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Clinical Microbiology Reviews Dec 2019is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This... (Review)
Review
is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This capacity has helped the fungus to resist and survive against human host defenses and, further, to be responsible for one of the most devastating lung infections in terms of morbidity and mortality. In this review, we will provide (i) a description of the biological cycle of ; (ii) a historical perspective of the spectrum of aspergillus disease and the current epidemiological status of these infections; (iii) an analysis of the modes of immune response against in immunocompetent and immunocompromised patients; (iv) an understanding of the pathways responsible for fungal virulence and their host molecular targets, with a specific focus on the cell wall; (v) the current status of the diagnosis of different clinical syndromes; and (vi) an overview of the available antifungal armamentarium and the therapeutic strategies in the clinical context. In addition, the emergence of new concepts, such as nutritional immunity and the integration and rewiring of multiple fungal metabolic activities occurring during lung invasion, has helped us to redefine the opportunistic pathogenesis of .
Topics: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Disease Susceptibility; History, 21st Century; Host-Pathogen Interactions; Humans; Immunity; Immunocompromised Host; Public Health Surveillance; Treatment Outcome; Virulence
PubMed: 31722890
DOI: 10.1128/CMR.00140-18 -
Virulence Dec 2023Pulmonary infections caused by the mould pathogen are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression,... (Review)
Review
Pulmonary infections caused by the mould pathogen are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression, chronic respiratory conditions or more recently, concomitant viral or bacterial pulmonary infections are recognised risks factors for the development of pulmonary aspergillosis. In this review, we will summarise our current knowledge of the mechanistic basis of pulmonary aspergillosis with a focus on emerging at-risk populations.
Topics: Humans; Aspergillus fumigatus; Virulence; Aspergillosis; Virulence Factors; Pulmonary Aspergillosis
PubMed: 36752587
DOI: 10.1080/21505594.2023.2172264 -
Allergology International : Official... Oct 2023Fungal sensitization is highly prevalent in severe asthma. The relationship between fungus and asthma, especially Aspergillus fumigatus, has been the subject of... (Review)
Review
Fungal sensitization is highly prevalent in severe asthma. The relationship between fungus and asthma, especially Aspergillus fumigatus, has been the subject of extensive research. The ubiquitous presence of A. fumigatus, its thermotolerant nature, the respirable size of its conidia, and its ability to produce potent allergens are pivotal in worsening asthma control. Due to the diverse clinical manifestations of fungal asthma and the lack of specific biomarkers, its diagnosis remains intricate. Diagnosing fungal asthma requires carefully assessing the patient's clinical history, immunological tests, and imaging. Depending on the severity, patients with fungal asthma require personalized treatment plans, including inhaled corticosteroids and bronchodilators, and antifungal therapy. This review provides a comprehensive overview of the association between Aspergillus and asthma by reviewing the relevant literature and highlighting key findings. We discuss the diagnosis of various entities included in fungal asthma. We also debate whether newer definitions, including allergic fungal airway disease, offer any additional advantages over the existing ones. Finally, we provide the current treatment options for the individual entities, including A. fumigatus-associated asthma, severe asthma with fungal sensitization, and allergic bronchopulmonary mycoses.
Topics: Humans; Aspergillosis, Allergic Bronchopulmonary; Asthma; Aspergillus fumigatus; Allergens; Respiratory System; Mycoses
PubMed: 37633774
DOI: 10.1016/j.alit.2023.08.004 -
Mycopathologia Oct 2023Aspergillus fumigatus is one the most ubiquitous airborne opportunistic human fungal pathogens. Understanding its interaction with host immune system, composed of... (Review)
Review
Aspergillus fumigatus is one the most ubiquitous airborne opportunistic human fungal pathogens. Understanding its interaction with host immune system, composed of cellular and humoral arm, is essential to explain the pathobiology of aspergillosis disease spectrum. While cellular immunity has been well studied, humoral immunity has been poorly acknowledge, although it plays a crucial role in bridging the fungus and immune cells. In this review, we have summarized available data on major players of humoral immunity against A. fumigatus and discussed how they may help to identify at-risk individuals, be used as diagnostic tools or promote alternative therapeutic strategies. Remaining challenges are highlighted and leads are given to guide future research to better grasp the complexity of humoral immune interaction with A. fumigatus.
Topics: Humans; Aspergillus fumigatus; Immunity, Humoral; Aspergillosis
PubMed: 37289362
DOI: 10.1007/s11046-023-00742-0 -
Intensive Care Medicine Sep 2021
Topics: Abscess; Aspergillosis; Aspergillus fumigatus; COVID-19; Humans; SARS-CoV-2
PubMed: 34100972
DOI: 10.1007/s00134-021-06440-z -
FEBS Letters Aug 2020Aspergillosis is a life-threatening infection mostly affecting immunocompromised individuals and primarily caused by the saprophytic fungus Aspergillus fumigatus. At... (Review)
Review
Aspergillosis is a life-threatening infection mostly affecting immunocompromised individuals and primarily caused by the saprophytic fungus Aspergillus fumigatus. At the host-pathogen interface, both cellular and humoral components of the innate immune system are increasingly acknowledged as essential players in the recognition and disposal of this opportunistic mold. Fundamental hereof is the contribution of the complement system, which deploys all three activation pathways in the battle against A. fumigatus, and functionally cooperates with other soluble pattern recognition molecules, including pentraxins. In particular, preclinical and clinical observations point to the long pentraxin PTX3 as a nonredundant and complement-dependent effector with protective functions against A. fumigatus. Based on past and current literature, here we discuss how the complement participates in the immune response to this fungal pathogen, and illustrate its crosstalk with the pentraxins, with a focus on PTX3. Emphasis is placed on the molecular mechanisms underlying such processes, the genetic evidence from human epidemiology, and the translational potential of the currently available knowledge.
Topics: Animals; Aspergillosis; Aspergillus fumigatus; C-Reactive Protein; Complement System Proteins; Humans; Serum Amyloid P-Component
PubMed: 31994174
DOI: 10.1002/1873-3468.13744 -
Current Protocols in Microbiology Sep 2019Aspergillus fumigatus is an opportunistic human fungal pathogen, capable of causing invasive aspergillosis in patients with compromised immune systems. The fungus was...
Aspergillus fumigatus is an opportunistic human fungal pathogen, capable of causing invasive aspergillosis in patients with compromised immune systems. The fungus was long considered a purely asexual organism. However, a sexual cycle was reported in 2009, with methods described to induce mating under laboratory conditions. The presence of a sexual cycle now offers a valuable tool for classical genetic analysis of the fungus, such as allowing determination of whether traits of interest are mono- or poly-genic in nature. For example, the sexual cycle is currently being exploited to determine the genetic basis of traits of medical importance such as resistance to azole antifungals and virulence, and to characterize the genes involved. The sexual cycle can also be used to assess the possibility of gene flow between isolates. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This unit describes protocols for culturing of A. fumigatus and for inducing sexual reproduction between compatible MAT1-1 and MAT1-2 isolates of the species. The unit also provides working methods for harvesting sexual structures, isolating single-spore progeny and confirming whether sexual recombination has occurred. © The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Topics: Aspergillosis; Aspergillus fumigatus; Culture Media; Genes, Mating Type, Fungal; Humans; Mycology; Polymerase Chain Reaction; Preservation, Biological; Spores, Fungal
PubMed: 31518066
DOI: 10.1002/cpmc.87 -
Cell Host & Microbe Mar 2023The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning...
The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on conidia-containing phagosomes (PSs), excludes the PS maturation mediator Rab7, and triggers binding of exocytosis mediators Rab11 and Sec15. This reprogramming redirects PSs to the non-degradative pathway, allowing A. fumigatus to escape cells by outgrowth and expulsion as well as transfer of conidia between cells. The clinical relevance is supported by the identification of a single nucleotide polymorphism in the non-coding region of the S100A10 (p11) gene that affects mRNA and protein expression in response to A. fumigatus and is associated with protection against invasive pulmonary aspergillosis. These findings reveal the role of p11 in mediating fungal PS evasion.
Topics: Animals; Humans; Aspergillus fumigatus; Phagosomes; Endosomes; Spores, Fungal; Mammals
PubMed: 36893734
DOI: 10.1016/j.chom.2023.02.002 -
Nature Dec 2020Inflammasomes are important sentinels of innate immune defence that are activated in response to diverse stimuli, including pathogen-associated molecular patterns...
Inflammasomes are important sentinels of innate immune defence that are activated in response to diverse stimuli, including pathogen-associated molecular patterns (PAMPs). Activation of the inflammasome provides host defence against aspergillosis, which is a major health concern for patients who are immunocompromised. However, the Aspergillus fumigatus PAMPs that are responsible for inflammasome activation are not known. Here we show that the polysaccharide galactosaminogalactan (GAG) of A. fumigatus is a PAMP that activates the NLRP3 inflammasome. The binding of GAG to ribosomal proteins inhibited cellular translation machinery, and thus activated the NLRP3 inflammasome. The galactosamine moiety bound to ribosomal proteins and blocked cellular translation, which triggered activation of the NLRP3 inflammasome. In mice, a GAG-deficient Aspergillus mutant (Δgt4c) did not elicit protective activation of the inflammasome, and this strain exhibited enhanced virulence. Moreover, administration of GAG protected mice from colitis induced by dextran sulfate sodium in an inflammasome-dependent manner. Thus, ribosomes connect the sensing of this fungal PAMP to the activation of an innate immune response.
Topics: Animals; Aspergillosis; Aspergillus fumigatus; Biofilms; Colitis; Dextran Sulfate; Female; Fungal Proteins; Gene Deletion; Immunity, Innate; Inflammasomes; Male; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Pathogen-Associated Molecular Pattern Molecules; Polysaccharides; Protein Biosynthesis; Ribosomal Proteins; Ribosomes
PubMed: 33268895
DOI: 10.1038/s41586-020-2996-z -
MBio Aug 2021Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs...
Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilization of acetate as a carbon source by fungi in the context of infection has not been investigated. This work shows that acetate is metabolized via different pathways in A. fumigatus and that acetate utilization is under the regulatory control of a transcription factor (TF), FacB. A. fumigatus acetate utilization is subject to carbon catabolite repression (CCR), although this is only partially dependent on the TF and main regulator of CCR CreA. The available extracellular carbon source, in this case glucose and acetate, significantly affected A. fumigatus virulence traits such as secondary metabolite secretion and cell wall composition, with the latter having consequences for resistance to oxidative stress, antifungal drugs, and human neutrophil-mediated killing. Furthermore, deletion of significantly impaired the virulence of A. fumigatus in both insect and mammalian models of invasive aspergillosis. This is the first report on acetate utilization in A. fumigatus, and this work further highlights the importance of available host-specific carbon sources in shaping fungal virulence traits and subsequent disease outcome, and a potential target for the development of antifungal strategies. Aspergillus fumigatus is an opportunistic fungal pathogen in humans. During infection, A. fumigatus is predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonization and invasion. This work shows that A. fumigatus metabolizes acetate via different pathways, a process that is dependent on the transcription factor FacB. Furthermore, the type and concentration of the extracellular available carbon source were determined to shape A. fumigatus virulence determinants such as secondary metabolite secretion and cell wall composition. Subsequently, interactions with immune cells are altered in a carbon source-specific manner. FacB is required for A. fumigatus virulence in both insect and mammalian models of invasive aspergillosis. This is the first report that characterizes acetate utilization in A. fumigatus and highlights the importance of available host-specific carbon sources in shaping virulence traits and potentially subsequent disease outcome.
Topics: Acetates; Animals; Aspergillosis; Aspergillus fumigatus; Fungal Proteins; Gene Expression Regulation, Fungal; Humans; Larva; Male; Mice; Mice, Inbred C57BL; Moths; Neutrophils; Phenotype; Secondary Metabolism; Virulence
PubMed: 34311583
DOI: 10.1128/mBio.01682-21