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At least 19 recordsLinked to original sources
PubMed2003

Aspergillosis caused by non-fumigatus Aspergillus species: risk factors and in vitro susceptibility compared with Aspergillus fumigatus.

Invasive aspergillosis (IA) caused by inherently more antifungal-resistant non-fumigatus Aspergillus species has become an important life-threatening complication in severely immunocompromised patients with cancer. The purpose of this study was to compare the relative incidence of, risk factors for, and in vitro correlation of amphotericin B and itraconazole with the clinical outcome of IA caused by Aspergillus fumigatus with those of IA caused by non-fumigatus Aspergillus spp. in patients with cancer. A retrospective search of our tertiary care cancer center's microbiology laboratory reports from 1998-2001 revealed 40 patients with cancer and IA. A non-fumigatus Aspergillus species caused IA in 28 (70%) of those patients. A. fumigatus was the predominant cause of late-onset IA after bone marrow transplantation (p = 0.05), whereas IA due to non-fumigatus Aspergillus spp. was more common in patients with neutropenia (p = 0.01). The minimum inhibitory concentration (50/90) and minimum fungicidal concentration (50/90) for amphotericin B were higher in the non-fumigatus Aspergillus spp. group than in the A. fumigatus one. The Aspergillus species distribution in IA cases in our institution shows a predominance of the more antifungal-resistant or -tolerant non-fumigatus Aspergillus spp.

Adult↗
PubMed2006

Intrinsic in vitro susceptibility of primary clinical isolates of Aspergillus fumigatus, Aspergillus terreus, Aspergillus nidulans, Candida albicans and Candida lusitaniae against amphotericin B.

A total of 60 clinical fungal isolates from patients without prior amphotericin B treatment and three control strains were evaluated for their intrinsic susceptibility to amphotericin B (AmB) using microdilution, Etest and disc diffusion assays, on three media each, Roswell Park Memorial Institute (RPMI) 1640, Antibiotic Medium 3 (AM3) and High Resolution Medium. The fungal strains included isolates of Aspergillus fumigatus (n = 10), Aspergillus terreus (n = 12), Aspergillus nidulans (n = 9), Candida albicans (n = 6) and Candida lusitaniae (n = 23). The A. terreus strains were significantly less susceptible to AmB than the A. fumigatus strains in all nine experimental settings (P-values ranging from 0.009 to <0.00001). The A. nidulans strains were equally susceptible to AmB as the A. fumigatus strains in seven of nine experimental settings and less susceptible in two (microdilution performed on RPMI and AM3, P = 0.01 and 0.007). The C. lusitaniae strains were equally susceptible to AmB as the C. albicans strains in seven of nine experimental settings and more susceptible in two (microdilution and Etest, both performed on AM3, P = 0.01 and 0.0002). Thus, we confirmed that A. terreus is intrinsically less susceptible to AmB than A. fumigatus. In contrast, nine German clinical isolates of Aspergillus nidulans were found equally susceptible to AmB as 10 isolates of A. fumigatus. Furthermore, we found 23 German clinical isolates of C. lusitaniae from patients without prior treatment with AmB equally susceptible to AmB as C. albicans.

Amphotericin B↗
PubMed2004

Elastase and elastase inhibitor from Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger.

Elastolytic and elastase inhibitory activities were investigated for 13 strains of Aspergillus fumigatus, three strains of Aspergillus flavus and three strains of Aspergillus niger. Nine of the 13 strains of A. fumigatus and all strains of A. flavus demonstrated elastase activity (more than 1 unit ml(-1)). Six of the 13 strains of A. fumigatus and all strains of A. flavus expressed elastase inhibitory activity (more than 2 units ml(-1)). However, no elastase or elastase inhibitory activities were observed with A. niger. It was also found that crude elastase inhibitors from six strains of A. fumigatus and two strains of A. flavus were stable to heat treatment at 100 degrees C for 10 min. In addition, human leukocyte elastases were inhibited by crude elastase inhibitors from A. fumigatus and A. flavus; however, no effect was observed on the elastase derived from porcine pancreas.

Animals↗
PubMed2004

PCR identification system for the genus Aspergillus and three major pathogenic species: Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger.

A PCR system was developed that allowed recognition of three major pathogenic Aspergillus species, namely A. fumigatus, A. niger and A. flavus, in isolates obtained from clinical specimens. The primer pair for PCR was designed from conserved sequences of internal transcribed spacer 1 (ITS1) ribosomal DNA and its flanking regions. Products 521 bp in size were successfully amplified by PCR from the seven Aspergillus species most frequently encountered as opportunistic pathogens, and the three most commonly significant species were identified by separate PCR reactions or nested PCR based on use of species-specific primers. To our knowledge, this is first report of identification of the second and third most frequent pathogenic Aspergillus species using specific PCR amplification. The PCR based identification system reported here will be a powerful tool to control difficult pulmonary fungal infections and to speed the application of effective treatment.

Aspergillus flavus↗
PubMed2006

A nonribosomal peptide synthetase (Pes1) confers protection against oxidative stress in Aspergillus fumigatus.

Aspergillus fumigatus is an important human fungal pathogen. The Aspergillus fumigatus genome contains 14 nonribosomal peptide synthetase genes, potentially responsible for generating metabolites that contribute to organismal virulence. Differential expression of the nonribosomal peptide synthetase gene, pes1, in four strains of Aspergillus fumigatus was observed. The pattern of pes1 expression differed from that of a putative siderophore synthetase gene, sidD, and so is unlikely to be involved in iron acquisition. The Pes1 protein (expected molecular mass 698 kDa) was partially purified and identified by immunoreactivity, peptide mass fingerprinting (36% sequence coverage) and MALDI LIFT-TOF/TOF MS (four internal peptides sequenced). A pes1 disruption mutant (delta pes1) of Aspergillus fumigatus strain 293.1 was generated and confirmed by Southern and western analysis, in addition to RT-PCR. The delta pes1 mutant also showed significantly reduced virulence in the Galleria mellonella model system (P < 0.001) and increased sensitivity to oxidative stress (P = 0.002) in culture and during neutrophil-mediated phagocytosis. In addition, the mutant exhibited altered conidial surface morphology and hydrophilicity, compared to Aspergillus fumigatus 293.1. It is concluded that pes1 contributes to improved fungal tolerance against oxidative stress, mediated by the conidial phenotype, during the infection process.

Aspergillus fumigatus↗
PubMed1986

Inhibition of complement by culture supernatants of Aspergillus fumigatus.

Aspergillus fumigatus produced a water-soluble extracellular material that inhibited the opsonization of fungal cells by normal human serum. Blastospores of Cryptococcus neoformans and conidia from A. fumigatus or Aspergillus niger were used as fungal targets for ingestion by human monocytes. The opsonic inhibitor from A. fumigatus was found to decrease binding of complement component C3b to fungal surfaces by selectively interfering with activation of the alternative complement pathway. Inhibition of complement did not appear to result simply from proteolysis, as judged by the minimal degradation of casein and of purified C3 and C4. The complement-inhibiting activity was partially labile to heating at 100 C and could be concentrated by using dialysis tubing with a 10,000-dalton exclusion limit. Aspergillus flavus, which is also a pathogen for humans, also produced this activity; A. niger did not. We speculate that this material may represent a pathogenesis factor for Aspergillus species.

Aspergillus fumigatus↗
PubMed2003

Genetic variability and reproductive mode of Aspergillus fumigatus.

Aspergillus fumigatus, an important human pathogen, has been the subject of numerous epidemiological studies. This review gives a summary of the techniques used for revealing the genetic variability of A. fumigatus, including multilocus enzyme electrophoresis and methods based on DNA hybridization and amplification. Such studies have provided raw data for examining the structure of A. fumigatus populations. Several methods have been described for distinguishing recombination from clonality in fungal populations. In our studies, both the index of association test and the parsimony tree length permutation test were used for examining the reproductive mode of Aspergillus fumigatus populations. The tests were performed on isoenzyme and sequence specific DNA primer analysis data gathered from the literature. Both tests, together with other observations, supported the premise that recombination played an important role in A. fumigatus populations. A so-called epidemic population structure was observed in local populations isolated from patients. The prevalence of a single or some related electrophoretic types in such environments was attributed to some kind of selection pressure. Network methods were also used successfully to visualize the recombining structures of A. fumigatus populations. The applied techniques did not enable us to distinguish between the alternative hypotheses of whether past meiotic exchanges, parasexuality or a cryptic sexual stage were responsible for the recombining population structure of A. fumigatus.

Aspergillus fumigatus↗
PubMedDate not supplied

Use of phenotypic and genotypic fingerprinting methods in the strain identification of Aspergillus fumigatus.

Aspergillus fumigatus isolates (n = 6) from a lung transplant recipient, one isolate from a patient who had been on the same ward and a reference strain (NCPF 2140) were compared using three typing methods: SDS-PAGE, immunoblotting with serum from the transplant patient and random amplified polymorphic DNA (RAPD) assay. Neither the SDS-PAGE, immunoblot nor RAPD assay with single primers revealed differences between the eight isolates. Digestion of one primer product with the endonuclease EcoRI discriminated between the six patient isolates and the other two strains. The RAPD assay using pairwise combined primers showed identical patterns for the patient's strains but differentiated between the two other strains. It is concluded that any single technique may fail to detect strain differences and that a spectrum of typing methods is necessary in order to reveal or to exclude cross-infections with Aspergillus fumigatus.

Aspergillus fumigatus↗
PubMed2006

Functional genomics of innate host defense molecules in normal human monocytes in response to Aspergillus fumigatus.

Aspergillus fumigatus induces the release of innate immune-related molecules from phagocytic cells early in the course of infection. Little is known, however, about the complex expression profiles of the multiple genes involved in this response. We therefore investigated the kinetics of early gene expression in human monocytes (HMCs) infected with conidia of A. fumigatus using DNA microarray analysis. Total RNA from HMCs at 0, 2, 4, and 6 h was extracted, linearly amplified, hybridized onto Affymetrix HG133 Plus 2.0 gene chips, and analyzed with an Affymetrix scanner. Changes in gene expression were calculated as a ratio of those expressed by infected versus control HMCs. Aspergillus fumigatus induced differential regulation of expression in 1,827 genes (P < 0.05). Genes encoding cytokines and chemokines involved in host defense against A. fumigatus, including interleukin-1beta (IL-1beta), IL-8, CXCL2, CCL4, CCL3, and CCL20, as well as the opsonin long pentraxin 3, were up-regulated during the first 2 to 6 h, coinciding with an increase in phagocytosis. Simultaneously, genes encoding CD14, ficolin1, and MARCO were down-regulated, and genes encoding IL-10 and matrix metalloproteinase 1 were up-regulated. Up-regulation of the genes encoding heat shock proteins 40 and 110 and connexins 26 and 30 may point to novel molecules whose role in the pathogenesis of aspergillosis has not been previously reported. Verification of the transcriptional profiling was obtained for selected genes by reverse transcription-PCR and enzyme immunoassay. Thus, A. fumigatus conidia induced a coordinated expression of genes important in host defense and immunomodulation.

Aspergillosis↗
PubMed1998

Lacrimal sac plugging caused by Aspergillus fumigatus.

Aspergillus fumigatus is a rare cause of canalicular obstruction. We present a case where an aspergillosis plug caused extreme tenderness, epiphoria and discharge from the lacrimal puntum. CT scan showed dilation of the lacrimal sac. Medical treatment did not relieve the symptoms. During a planned DCR the sac was opened before the osteotomy, and found to contain a plug which caused the obstruction. Aspergillus fumigatus was grown from culture. The DCR was abandoned and the patient is symptom free one year after the procedure.

Adult↗
PubMed1991

Isolation and characterisation of an extracellular alkaline protease of Aspergillus fumigatus.

Aspergillus fumigatus secreted an inducible alkaline protease (AlPase) when cultivated in the presence of collagen (200 micrograms/ml) as sole nitrogen and carbon source. Proteolytic activity was maximum at pH 9.0 with azocollagen as substrate. The enzyme, which was the major protein found in the supernate of a liquid culture, was purified by ammonium sulphate precipitation and gel filtration. The Mr was determined to be 33 Kda by gel filtration and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The isoelectric point was estimated to be pH 8.2. Divalent cations strongly inhibited enzyme activity, whereas non-ionic detergents and reducing agents had no effect. A. fumigatus AlPase was totally inhibited by phenylmethanesulphonyl fluoride, antipain, chymostatin and alpha-2-macroglobulin. A. fumigatus AlPase is closely related to the A. oryzae AlPase, a serine protease of the subtilisin family, as attested by the antigen pattern seen by immunoblotting. The high collagenic activity and the ability of A. fumigatus AlPase to digest elastin could play a role in the invasion of the tissues by the fungus.

Aspergillus fumigatus↗
PubMed2005

Genomics of Aspergillus fumigatus.

Aspergillus fumigatus is a filamentous fungal saprophyte that is ubiquitous in the environment. It is also a human pathogen and induces allergenic response, negatively impacting health care and associated costs significantly around the world. Much of the basic biology of this organism is only poorly understood, but the recent completion and publication of its genome sequence provides an excellent tool for researchers to gain insight into these processes. In this review we will summarize some of the more salient features revealed by analysis of the genome, including the search for candidate pathogenicity genes and the switch to a pathogenic lifestyle, allergen proteins, DNA repair, secondary metabolite gene clusters that produce compounds both useful and toxic, a theoretical capability of this asexual organism to reproduce sexually, signalling, and transcription. A. fumigatus was compared with the food biotechnology fungus Aspergillus oryzae and sexual fungus Aspergillus nidulans, as well as other fungi, in an attempt to discern key differences between these organisms.

Allergens↗
PubMed2001

The pathobiology of Aspergillus fumigatus.

Aspergillus fumigatus is the most prevalent airborne fungal pathogen in developed countries, and in immunocompromised patients causes a usually fatal invasive aspergillosis (IA). Understanding the pathobiology of this fungal species requires not only analysis of the putative fungal virulence factors that stimulate fungal growth and/or survival in the lung environment, but also knowledge of the immune factors containing A. fumigatus in the immunocompetent host that can be debilitated by immunosuppressive therapies, triggering IA. Although the incidence of IA has dramatically increased in recent years, progress in these areas has been limited and, as yet, a single, true virulence factor has not been identified and the mechanisms responsible for protective immunity against A. fumigatus have yet to be elucidated.

Animals↗
PubMed2004

The cyclic AMP-dependent protein kinase a network regulates development and virulence in Aspergillus fumigatus.

Aspergillus fumigatus is an important pathogen of immunocompromised hosts, causing pneumonia and invasive disseminated disease with high mortality. To determine the importance of the cyclic AMP (cAMP) signaling pathway for virulence, the pkaC1 gene encoding a protein kinase A (PKA) catalytic subunit was cloned and characterized. Deletion of pkaC1 led to reduced conidiation and growth. PKA activity was not detectable in DeltapkaC1, DeltagpaB, and DeltaacyA mutant strains. gpaB and acyA encode a G protein alpha subunit involved in cAMP signal transduction and adenylate cyclase, respectively. Addition of cAMP led to PKA activity in crude extracts of both the DeltagpaB and DeltaacyA strains but not in crude extracts of the DeltapkaC1 strain. These findings provide evidence that PKAC1 represents the predominant form of PKA under the conditions tested, and GPAB and ACYA are members of the cAMP signaling cascade. Analysis of a pksPp-lacZ gene fusion indicated that the expression of the pathogenicity determinant-encoding pksP gene was reduced in DeltapkaC1 mutant strains compared with the expression of the gene fusion in the parental strain. In a low-dose murine inhalation model, conidia of both the DeltapkaC1 and DeltagpaB mutant strains were almost avirulent. Taken together, these findings indicate that the cAMP-PKA signal transduction pathway is required for A. fumigatus pathogenicity.

Animals↗
PubMed2005

Intracellular and extracellular growth of Aspergillus fumigatus.

Aspergillus fumigatus is a filamentous fungus that can cause a life-threatening systemic mycosis in immunocompromised patients. We have studied the growth of A. fumigatus inside cultured cells, and the extracellular growth requirements (in serum). We measured the uptake of bound conidia by the cultured human type II pneumocyte cell line (A549) and a mouse macrophage cell line (J774). The extent of internalization was determined using a nystatin protection assay and by confocal microscopy. Both assays showed that A549 cells internalized 30% of bound conidia after three hours. In contrast, the value for J774 cells was 90%. In both J774 and A549 cells, conidia entered the endosomal pathway and ultimately co-localized with lysosomal markers. Lysosomes containing conidia were acidified. Internalized conidia germinated, and after 24-36 h of incubation with A549 cells, the hyphal tips of some intracellular germlings became exposed to the extracellular space. The importance of iron acquisition to extracellular growth was assessed by creating a strain of A. fumigatus in which the gene encoding the first step of hydroxamate siderophore biosynthesis, ornithine N5-oxygenase (AfusidA), was inactivated by gene replacement. Mutant strains were avirulent in a mouse model of invasive aspergillosis indicating that siderophore biosynthesis is a virulence factor in A. fumigatus.

Animals↗
PubMed2026

Functional characterization of SHC-like triterpene cyclase genes in azole response and virulence-related traits of Aspergillus fumigatus.

Aspergillus fumigatus is a major opportunistic fungal pathogen, and increasing azole resistance poses a challenge for aspergillosis treatment. Squalene is an upstream precursor of ergosterol biosynthesis and may also be utilized by SHC-like triterpene cyclases, suggesting a potential link between squalene-associated metabolism, membrane adaptation, and azole response. However, the roles of SHC-like triterpene cyclase genes in A. fumigatus remain unclear. Here, we characterized three candidates, shc1, shc2, and shc3, using comparative bioinformatic analysis, gene deletion, phenotypic assays, azole susceptibility testing, transcriptomics, and host-interaction models. Sequence, genomic-context, phylogenetic, and structural analyses suggested divergence among the three candidates. Individual shc deletion caused limited effects on vegetative growth, whereas loss of shc1 mildly reduced susceptibility to voriconazole and posaconazole, as reflected by twofold MIC increases and lower inhibition rates. Transcriptomic analysis revealed distinct remodeling patterns, with &#x394;shc3 showing the broadest transcriptional changes despite no detectable MIC shift. Targeted metabolite profiling and PI uptake analysis further supported an association between shc deletion, sterol/hopane-type triterpenoid balance, and membrane-associated properties. shc deletion also altered epithelial cell interaction phenotypes, while &#x394;shc1 showed reduced lethality in Galleria mellonella. In clinical isolates, elevated shc transcription was associated with azole-resistant backgrounds. These findings suggest functional diversification among SHC-like triterpene cyclase genes and indicate that shc1 may contribute to azole-associated adaptation and virulence-related traits in A. fumigatus.

Aspergillus fumigatus↗