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Clinical Microbiology Reviews Apr 1999Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia... (Review)
Review
Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.
Topics: Animals; Antigens, Fungal; Aspergillosis; Aspergillus fumigatus; Disease Models, Animal; Humans; Serologic Tests; Virulence
PubMed: 10194462
DOI: 10.1128/CMR.12.2.310 -
Cold Spring Harbor Perspectives in... Nov 2014The genus Aspergillus contains etiologic agents of aspergillosis. The clinical manifestations of the disease range from allergic reaction to invasive pulmonary... (Review)
Review
The genus Aspergillus contains etiologic agents of aspergillosis. The clinical manifestations of the disease range from allergic reaction to invasive pulmonary infection. Among the pathogenic aspergilli, Aspergillus fumigatus is most ubiquitous in the environment and is the major cause of the disease, followed by Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Aspergillus nidulans, and several species in the section Fumigati that morphologically resemble A. fumigatus. Patients that are at risk for acquiring aspergillosis are those with an altered immune system. Early diagnosis, species identification, and adequate antifungal therapy are key elements for treatment of the disease, especially in cases of pulmonary invasive aspergillosis that often advance very rapidly. Incorporating knowledge of the basic biology of Aspergillus species to that of the diseases that they cause is fundamental for further progress in the field.
Topics: Aspergillus fumigatus; Humans; Invasive Pulmonary Aspergillosis
PubMed: 25377144
DOI: 10.1101/cshperspect.a019786 -
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 -
Canadian Journal of Microbiology Jul 2018The genus Aspergillus includes fungal species that cause major health issues of significant economic importance. These microorganisms are also the culprit for production... (Review)
Review
The genus Aspergillus includes fungal species that cause major health issues of significant economic importance. These microorganisms are also the culprit for production of carcinogenic aflatoxins in grain storages, contaminating crops, and economically straining the production process. Aspergillus fumigatus is a very important pathogenic species, being responsible for high human morbidity and mortality on a global basis. The prevalence of these infections in immunosuppressed individuals is on the rise, and physicians struggle with the diagnosis of these deadly pathogens. Several virulence determinants facilitate fungal invasion and evasion of the host immune response. Metabolic functions are also important for virulence and drug resistance, since they allow fungi to obtain nutrients for their own survival and growth. Following a positive diagnostic identification, mortality rates remain high due, in part, to emerging resistance to frequently used antifungal drugs. In this review, we discuss the role of the main virulence, drug target, and drug resistance determinants. We conclude with the review of new technologies being developed to treat aspergillosis. In particular, microsphere and nanoparticle delivery systems are discussed in the context of improving drug bioavailability. Aspergillus will likely continue to cause problematic infections in immunocompromised patients, so it is imperative to improve treatment options.
Topics: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Drug Resistance, Fungal; Humans; Immunocompromised Host; Nanoparticles; Virulence; Virulence Factors
PubMed: 29586541
DOI: 10.1139/cjm-2017-0749 -
Current Protein & Peptide Science 2014Incidence of fungal infections has increased alarmingly in past few decades. Of the fungal pathogens, the Aspergillus fumigatus has been a major cause of allergic... (Review)
Review
Incidence of fungal infections has increased alarmingly in past few decades. Of the fungal pathogens, the Aspergillus fumigatus has been a major cause of allergic bronchopulmonary aspergillosis (ABPA) which has five main stages--the acute, remission, exacerbation, glucocorticoid dependent and fibrotic stage. The diagnosis of ABPA remains difficult due to its overlapping clinical and radiological features with tuberculosis and cystic fibrosis. From past few decades, the crude fractions of A. fumigatus have been used for immunodiagnosis of ABPA. Most of the detection kits based on crude fractions of A. fumigatus are quite sensitive but have low specificity. Till date 21 known and 25 predicted allergens of A. fumigatus have been identified. Of these allergens, only five recombinants (rAsp f1-f4 and f6) are commercially used for diagnosis of allergic aspergillosis. Remaining allergens of A. fumigatus have been restricted for use in specific diagnosis of ABPA, due to sharing of common antigenic epitopes with other allergens. Complete sequencing of A. fumigatus genome identified 9926 genes and the reports on the proteome of A. fumigatus have shown the presence of large number of their corresponding proteins in the pathogen. The analysis of immunoproteomes developed from crude fractions of A. fumigatus by IgG/IgE reactivity with ABPA patients and animal sera have identified the panel of new antigens. A brief description on the current status of A. fumigatus antigens is provided in this review. The implementation of advance recombinant expression and peptidomic approaches on the A. fumigatus antigens may help in the selection of appropriate molecules for the development of tools for more specific early diagnosis of ABPA, and desensitization therapies for patients of allergic disorders.
Topics: Allergens; Animals; Antigens, Fungal; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Humans; Peptide Library; Proteomics
PubMed: 24818760
DOI: 10.2174/1389203715666140512120605 -
Current Opinion in Infectious Diseases Dec 2018Aspergillus fumigatus is a ubiquitous saprophytic fungus that can cause life-threatening invasive aspergillosis in immunocompromised patients. Apart from the immune... (Review)
Review
PURPOSE OF REVIEW
Aspergillus fumigatus is a ubiquitous saprophytic fungus that can cause life-threatening invasive aspergillosis in immunocompromised patients. Apart from the immune status of the host only a few characterized virulence factors have been identified. In this review, we describe the role of iron in the manifestation of A. fumigatus virulence.
RECENT FINDINGS
We gathered recent clinical evidence suggesting that tissue iron overload increases the risk of invasive aspergillosis occurrence. Furthermore, we summarize the mechanisms that A. fumigatus employs to achieve iron homeostasis and their importance in A. fumigatus proliferation in vitro. We describe two recent in-vivo models that clearly demonstrate the importance of iron in A. fumigatus growth and invasion.
SUMMARY
Based on these recent findings, therapy aimed at managing A. fumigatus iron homeostasis locally could make conditions more favorable to the host.
Topics: Aspergillosis; Aspergillus fumigatus; Humans; Immunocompromised Host; Iron; Iron Overload; Models, Biological; Risk Factors
PubMed: 30379731
DOI: 10.1097/QCO.0000000000000487 -
Virulence Dec 2021is the leading cause of life-threatening invasive mold infections in immunocompromised individuals. This ubiquitous saprophyte possesses several natural attributes...
is the leading cause of life-threatening invasive mold infections in immunocompromised individuals. This ubiquitous saprophyte possesses several natural attributes allowing it to evade the immune system, including the ability to withstand high toxic Cu concentrations within the phagosomes of macrophages and neutrophils. We previously established that at high levels, Cu binds and activates the transcription factor AceA, which upregulates the expression of the Cu exporter CrpA to expel excess Cu. Deletion of or result in extreme Cu sensitivity and attenuated virulence.To identify other elements participating in resistance to Cu, we performed a genome-wide analysis of the transcriptome by RNAseq to analyze the AceA-dependent response of to excess Cu. We deleted key genes whose transcription was strongly upregulated by high Cu, including those encoding homologs of the three Cu chaperones and . Detailed analysis of these genes indicates that in is an essential gene with a possible role in respiration, the gene product participates in reductive iron uptake and encodes the Cu chaperone activating Sod1. Interestingly, although the -null strain was extremely sensitive to high Cu and oxidative stress, it was not attenuated in virulence in a mouse model of invasive pulmonary aspergillosis.Our work provides (i) a detailed view of the genome-wide transcriptional response of to excess Cu, (ii) identification of the AceA-dependent transcriptome and (iii) analysis of the roles of the three Cu chaperones and
Topics: Animals; Aspergillus fumigatus; Copper; Fungal Proteins; Mice; Molecular Chaperones; Transcription Factors; Virulence
PubMed: 34468270
DOI: 10.1080/21505594.2021.1958057 -
Trends in Microbiology Jan 2013Species in the filamentous fungal genus Aspergillus display a wide diversity of lifestyles and are of great importance to humans. The decoding of genome sequences from a... (Review)
Review
Species in the filamentous fungal genus Aspergillus display a wide diversity of lifestyles and are of great importance to humans. The decoding of genome sequences from a dozen species that vary widely in their degree of evolutionary affinity has galvanized studies of the function and evolution of the Aspergillus genome in clinical, industrial, and agricultural environments. Here, we synthesize recent key findings that shed light on the architecture of the Aspergillus genome, on the molecular foundations of the genus' astounding dexterity and diversity in secondary metabolism, and on the genetic underpinnings of virulence in Aspergillus fumigatus, one of the most lethal fungal pathogens. Many of these insights dramatically expand our knowledge of fungal and microbial eukaryote genome evolution and function and argue that Aspergillus constitutes a superb model clade for the study of functional and comparative genomics.
Topics: Aspergillus fumigatus; Genetic Variation; Genome, Fungal; Humans; Industrial Microbiology; Molecular Epidemiology; Mycology; Virulence
PubMed: 23084572
DOI: 10.1016/j.tim.2012.09.005 -
Environmental Microbiology Dec 2020The ubiquitous fungal pathogen Aspergillus fumigatus is the primary cause of opportunistic mould infections in humans. Aspergilli disseminate via asexual conidia... (Review)
Review
The ubiquitous fungal pathogen Aspergillus fumigatus is the primary cause of opportunistic mould infections in humans. Aspergilli disseminate via asexual conidia passively travelling through air currents to germinate within a broad range of environs, wherever suitable nutrients are found. Though the average human inhales hundreds of conidia daily, A. fumigatus invasive infections primarily affect the immunocompromised. At-risk individuals can develop often fatal invasive disease for which therapeutic options are limited. Regrettably, the global insurgence of isolates resistant to the triazoles, the frontline antifungal class used in medicine and agriculture to control A. fumigatus, is complicating the treatment of patients. Triazole antifungal resistance in A. fumigatus has become recognized as a global, yet poorly comprehended, problem. Due to a multitude of factors, the magnitude of resistant infections and their contribution to treatment outcomes are likely underestimated. Current studies suggest that human drug-resistant infections can be either environmentally acquired or de novo host selected during patient therapy. While much concerning development of resistance is yet unknown, recent investigations have revealed assorted underlying mechanisms enabling triazole resistance within individual clinical and environmental isolates. This review will provide an overview of triazole resistance as it is currently understood, as well as highlight some of the prominent biological mechanisms associated with clinical and environmental resistance to triazoles in A. fumigatus.
Topics: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Drug Resistance, Fungal; Humans; Microbial Sensitivity Tests; Triazoles
PubMed: 33047482
DOI: 10.1111/1462-2920.15274 -
Microbiology Spectrum Aug 2015In vivo, Aspergillus fumigatus grows as a typical biofilm with hyphae covered by an extracellular matrix (ECM) composed of polysaccharides, galactomannan, and... (Review)
Review
In vivo, Aspergillus fumigatus grows as a typical biofilm with hyphae covered by an extracellular matrix (ECM) composed of polysaccharides, galactomannan, and galactosaminogalactan. α1,3 glucans and melanin are also constitutive of the ECM in aspergilloma but not in invasive aspergillosis. In vitro, two biofilm models were established to mimic the in vivo situation. The first model (model 1) uses submerged liquid conditions and is characterized by slow growth, while the second model (model 2) uses agar medium and aerial conditions and is characterized by rapid growth. The composition of the ECM was studied only in the second model and has been shown to be composed of galactomannan, galactosaminogalactan (GAG), and α1,3 glucans, melanin, antigens, and hydrophobins. The presence of extracellular DNA was detected in model 1 biofilm but not in model 2. Transcriptomic analysis employing both biofilm models showed upregulation of genes coding for proteins involved in the biosynthesis of secondary metabolites, adhesion, and drug resistance. However, most data on A. fumigatus biofilms have been obtained in vitro and should be confirmed using in vivo animal models. There is a need for new therapeutic antibiofilm strategies that focus on the use of combination therapy, since biofilm formation poses an important clinical problem due to their resistance to antifungal agents. Furthermore, in vivo investigations of A. fumigatus biofilms that incorporate the associated microbiota are needed. Such studies will add another layer of complexity to our understanding of the role of A. fumigatus biofilm during lung invasion.
Topics: Animals; Aspergillosis; Aspergillus fumigatus; Bacterial Proteins; Biofilms; Extracellular Matrix; Humans
PubMed: 26350307
DOI: 10.1128/microbiolspec.MB-0017-2015