-
Journal of Molecular Biology Oct 2019The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans... (Review)
Review
The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans inhale several hundred to several thousand Aspergillus conidia (i.e., vegetative spores) daily and typically clear these in an asymptomatic manner. In immunocompromised individuals, Aspergillus conidia can germinate into tissue-invasive hyphae, disseminate, and cause invasive aspergillosis. In this review, we first discuss novel concepts in host defense against Aspergillus infections and emphasize new insights in fungal recognition and signaling, innate immune activation, and fungal killing. Second, the review focuses on novel concepts of Aspergillus pathogenesis and highlights emerging knowledge regarding fungal strain heterogeneity, stress responses, and metabolic adaptations on infectious outcomes. Mechanistic insight into the host-pathogen interplay is thus critical to define novel druggable fungal targets and to exploit novel immune-based strategies to improve clinical outcomes associated with aspergillosis in vulnerable patient populations.
Topics: Animals; Aspergillosis; Aspergillus; Cell Wall; Humans; Immunity, Innate; Mycology
PubMed: 30954573
DOI: 10.1016/j.jmb.2019.03.027 -
Revista Chilena de Infectologia :... Aug 2019
Topics: Anti-Bacterial Agents; Aspergillus
PubMed: 31859778
DOI: 10.4067/S0716-10182019000400521 -
PLoS Genetics Jan 2022Aspergillus fumigatus causes a range of human and animal diseases collectively known as aspergillosis. A. fumigatus possesses and expresses a range of genetic... (Comparative Study)
Comparative Study
Aspergillus fumigatus causes a range of human and animal diseases collectively known as aspergillosis. A. fumigatus possesses and expresses a range of genetic determinants of virulence, which facilitate colonisation and disease progression, including the secretion of mycotoxins. Gliotoxin (GT) is the best studied A. fumigatus mycotoxin with a wide range of known toxic effects that impair human immune cell function. GT is also highly toxic to A. fumigatus and this fungus has evolved self-protection mechanisms that include (i) the GT efflux pump GliA, (ii) the GT neutralising enzyme GliT, and (iii) the negative regulation of GT biosynthesis by the bis-thiomethyltransferase GtmA. The transcription factor (TF) RglT is the main regulator of GliT and this GT protection mechanism also occurs in the non-GT producing fungus A. nidulans. However, the A. nidulans genome does not encode GtmA and GliA. This work aimed at analysing the transcriptional response to exogenous GT in A. fumigatus and A. nidulans, two distantly related Aspergillus species, and to identify additional components required for GT protection. RNA-sequencing shows a highly different transcriptional response to exogenous GT with the RglT-dependent regulon also significantly differing between A. fumigatus and A. nidulans. However, we were able to observe homologs whose expression pattern was similar in both species (43 RglT-independent and 11 RglT-dependent). Based on this approach, we identified a novel RglT-dependent methyltranferase, MtrA, involved in GT protection. Taking into consideration the occurrence of RglT-independent modulated genes, we screened an A. fumigatus deletion library of 484 transcription factors (TFs) for sensitivity to GT and identified 15 TFs important for GT self-protection. Of these, the TF KojR, which is essential for kojic acid biosynthesis in Aspergillus oryzae, was also essential for virulence and GT biosynthesis in A. fumigatus, and for GT protection in A. fumigatus, A. nidulans, and A. oryzae. KojR regulates rglT, gliT, gliJ expression and sulfur metabolism in Aspergillus species. Together, this study identified conserved components required for GT protection in Aspergillus species.
Topics: Aspergillus; Aspergillus fumigatus; Aspergillus nidulans; Aspergillus oryzae; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Gliotoxin; Methyltransferases; RNA-Seq; Transcription Factors
PubMed: 35041649
DOI: 10.1371/journal.pgen.1009965 -
Environmental Microbiology Jul 2022Post-translational modifications (PTMs) are important for protein function and regulate multiple cellular processes and secondary metabolites (SMs) in fungi. Aspergillus... (Review)
Review
Post-translational modifications (PTMs) are important for protein function and regulate multiple cellular processes and secondary metabolites (SMs) in fungi. Aspergillus species belong to a genus renown for an abundance of bioactive secondary metabolites, many important as toxins, pharmaceuticals and in industrial production. The genes required for secondary metabolites are typically co-localized in biosynthetic gene clusters (BGCs), which often localize in heterochromatic regions of genome and are 'turned off' under laboratory condition. Efforts have been made to 'turn on' these BGCs by genetic manipulation of histone modifications, which could convert the heterochromatic structure to euchromatin. Additionally, non-histone PTMs also play critical roles in the regulation of secondary metabolism. In this review, we collate the known roles of epigenetic and PTMs on Aspergillus SM production. We also summarize the proteomics approaches and bioinformatics tools for PTM identification and prediction and provide future perspectives on the emerging roles of PTM on regulation of SM biosynthesis in Aspergillus and other fungi.
Topics: Aspergillus; Fungi; Multigene Family; Protein Processing, Post-Translational; Secondary Metabolism
PubMed: 35645150
DOI: 10.1111/1462-2920.16034 -
Clinical Microbiology and Infection :... Aug 2016The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based... (Review)
Review
The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based identification of Aspergillus remains limited to the section or species-complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care.
Topics: Animals; Antifungal Agents; Aspergillosis; Aspergillus; Drug Resistance, Fungal; Genes, Fungal; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Population Surveillance; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 27263029
DOI: 10.1016/j.cmi.2016.05.013 -
Microbial Biotechnology Mar 2017Fungi of the genus Aspergillus are widespread in the environment. Some Aspergillus species, most commonly Aspergillus fumigatus, may lead to a variety of allergic... (Review)
Review
Fungi of the genus Aspergillus are widespread in the environment. Some Aspergillus species, most commonly Aspergillus fumigatus, may lead to a variety of allergic reactions and life-threatening systemic infections in humans. Invasive aspergillosis occurs primarily in patients with severe immunodeficiency, and has dramatically increased in recent years. There are several factors at play that contribute to aspergillosis, including both fungus and host-related factors such as strain virulence and host pulmonary structure/immune status, respectively. The environmental tenacity of Aspergilllus, its dominance in diverse microbial communities/habitats, and its ability to navigate the ecophysiological and biophysical challenges of host infection are attributable, in large part, to a robust stress-tolerance biology and exceptional capacity to generate cell-available energy. Aspects of its stress metabolism, ecology, interactions with diverse animal hosts, clinical presentations and treatment regimens have been well-studied over the past years. Here, we synthesize these findings in relation to the way in which some Aspergillus species have become successful opportunistic pathogens of human- and other animal hosts. We focus on the biophysical capabilities of Aspergillus pathogens, key aspects of their ecophysiology and the flexibility to undergo a sexual cycle or form cryptic species. Additionally, recent advances in diagnosis of the disease are discussed as well as implications in relation to questions that have yet to be resolved.
Topics: Animals; Aspergillosis; Aspergillus; Biophysical Phenomena; Diagnostic Tests, Routine; Ecosystem; Host-Pathogen Interactions; Humans
PubMed: 27273822
DOI: 10.1111/1751-7915.12367 -
Angewandte Chemie (International Ed. in... Oct 2021Drimane-type sesquiterpenes exhibit various biological activities and are widely present in eukaryotes. Here, we completely elucidated the biosynthetic pathway of the...
Drimane-type sesquiterpenes exhibit various biological activities and are widely present in eukaryotes. Here, we completely elucidated the biosynthetic pathway of the drimane-type sesquiterpene esters isolated from Aspergillus calidoustus and we discovered that it involves a drimenol cyclase having the same catalytic function previously only reported in plants. Moreover, since many fungal drimenol derivatives possess a γ-butyrolactone ring, we clarified the functions of the cluster-associated cytochrome P450 and FAD-binding oxidoreductase discovering that these two enzymes are solely responsible for the formation of those structures. Furthermore, swapping of the enoyl reductase domain in the identified polyketide synthase led to the production of metabolites containing various polyketide chains with different levels of saturation. These findings have deepened our understanding of how fungi synthesize drimane-type sesquiterpenes and the corresponding esters.
Topics: Aspergillus; Cytochrome P-450 Enzyme System; Esters; Oxidoreductases; Sesquiterpenes
PubMed: 34468074
DOI: 10.1002/anie.202108970 -
Molecules (Basel, Switzerland) Dec 2023Biotransformation of ursonic acid () by two fungal strains CGMCC 3.5324 and CGMCC 3.407 yielded thirteen new compounds (, , -, and -), along with five recognized ones....
Biotransformation of ursonic acid () by two fungal strains CGMCC 3.5324 and CGMCC 3.407 yielded thirteen new compounds (, , -, and -), along with five recognized ones. The structural details of new compounds were determined through spectroscopic examination (NMR, IR, and HR-MS) and X-ray crystallography. Various modifications, including hydroxylation, epoxidation, lactonization, oxygen introduction, and transmethylation, were identified on the ursane core. Additionally, the anti-neuroinflammatory efficacy of these derivatives was assessed on BV-2 cells affected by lipopolysaccharides. It was observed that certain methoxylated and epoxylated derivatives (, , and ) showcased enhanced suppressive capabilities, boasting IC values of 8.2, 6.9, and 5.3 μM. Such ursonic acid derivatives might emerge as potential primary molecules in addressing neurodegenerative diseases.
Topics: Aspergillus ochraceus; Aspergillus oryzae; Crystallography, X-Ray; Biotransformation
PubMed: 38138433
DOI: 10.3390/molecules28247943 -
Virulence 2011Conventional antineoplastic, novel immunosuppressive agents and antibiotics used in cancer treatment can directly affect the growth, development and virulence of Candida... (Review)
Review
Conventional antineoplastic, novel immunosuppressive agents and antibiotics used in cancer treatment can directly affect the growth, development and virulence of Candida and Aspergillus species. Cytotoxic and cisplatin compounds have anti-Candida activity and may be synergistic with antifungal drugs; they also inhibit Candida and Aspergillus filamentation/conidation and effect increased virulence in vitro. Glucocorticoids enhance Candida adherence to epithelial cells, germination in serum and in vitro secretion of phospholipases and proteases, as well as growth of A. fumigatus. Calcineurin and target of rapamycin inhibitors perturb Candida and Aspergillus morphogenesis, stress responses and survival in serum, reduce azole tolerance in Candida, but yield conflicting in vivo data. Inhibition of candidal heat shock protein 90 and candidal-specific histone deacetylase represent feasible therapeutic approaches for candidiasis. Tyrosine kinase inhibitors inhibit fungal cell entry into epithelial cells and phagocytosis. Quinolone and other antibiotics may augment activity of azole and polyene agents. The correlation of in vitro effects with clinically meaningful in vivo systems is warranted.
Topics: Animals; Antineoplastic Agents; Aspergillus; Candida albicans; Humans; Immunosuppressive Agents; Mycoses; Virulence
PubMed: 21701255
DOI: 10.4161/viru.2.4.16764 -
Annals of Agricultural and... Jun 2016Nosocomial invasive fungal infections, particularly aspergillosis, are an increasing problem in immunocompromised patients. The presented study evaluates fungal...
INTRODUCTION AND OBJECTIVE
Nosocomial invasive fungal infections, particularly aspergillosis, are an increasing problem in immunocompromised patients. The presented study evaluates fungal diversity and the presence of Aspergillus in air samples from two hospitals.
MATERIALS AND METHODS
Over the course of one year (rainy and dry seasons), the air was sampled from three areas in two hospitals (1 and 2) using a single-stage Andersen viable particle sampler (Thermo Scientific, Waltham, MA, USA). The fungi were identified by macro- and micromorphology, and the number of colony forming units (CFU)/m(3) air and their richness, abundance, and diversity were determined. Isolates Aspergillus genus were characterized by their thermotolerance.
RESULTS
The CFU/m(3) air was similar at both hospitals during the two seasons, but different between the sampled areas. Results showed 10 fungal genera for hospital 1, and 8 for hospital 2. The most abundant were Penicillium, Cladosporium and Aspergillus. The thermotolerance test confirmed the identification of A. fumigatus section Fumigati. The highest growth rate was found in Aspergillus section Nigri.
CONCLUSION
Determining the fungal diversity in the two hospitals was important because all the species have the potential to be pathogenic, especially the section Fumigati.
Topics: Air Microbiology; Air Pollution, Indoor; Aspergillus; Colony Count, Microbial; Environmental Microbiology; Fungi; Hospitals; Mexico; Seasons
PubMed: 27294630
DOI: 10.5604/12321966.1203888