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interactions of liposome carriers with infectious fungal hyphae reveals the role of β-glucans.relatively little is known about how liposomal formulations modulate drug delivery to fungal pathogens. we compared patterns of hyphal cell wall binding for empty rhodmine-labeled liposomes and the clinically available amphotericin b-containing liposomal formulation (ambisome) in aspergillus fumigatus and candida albicans. following 0.5 h of coincubation with a. fumigatus , empty liposomes concentrated primarily in fungal septae along at the surface of the cell wall, suggesting that liposome upt ...201222770505
aspergillus fumigatus keratitis following intracorneal ring segment implantation.fungal keratitis has been rarely reported following intracorneal ring segment (icrs) inmplantation. this paper aims to report a case of fungal keratitis with aspergillus fumigatus following icrs implantation for correction of keratoconus.201222769849
correlation between triazole treatment history and susceptibility in clinically isolated aspergillus fumigatus.this is the first report of a detailed relationship between triazole treatment history and triazole mics for 154 aspergillus fumigatus clinical isolates. the duration of itraconazole dosage increased as the itraconazole mic increased, and a positive correlation was observed (r = 0.5700, p < 0.0001). the number of itraconazole-naïve isolates dramatically decreased as the itraconazole mic increased, particularly for mics exceeding 2 μg/ml (0.5 μg/ml versus 2 μg/ml, p = 0.03). we also examined the ...201222751542
protein phosphatase z modulates oxidative stress response in fungi.the genome of the filamentous fungus aspergillus nidulans harbors the gene ppza that codes for the catalytic subunit of protein phosphatase z (ppz), and the closely related opportunistic pathogen aspergillus fumigatus encompasses a highly similar ppz gene (phza). when ppza and phza were expressed in saccharomyces cerevisiae or schizosaccharomyces pombe they partially complemented the deleted phosphatases in the ppz1 or the pzh1 mutants, and they also mimicked the effect of ppz1 overexpression in ...201222750657
[azole resistance in aspergillus fumigatus in the netherlands--increase due to environmental fungicides?].the mould aspergillus fumigatus may develop mechanisms that confer resistance to itraconazole, voriconazole and posaconazole. in the netherlands a dominant resistance mechanism referred to as tr/l98h is found. in a. fumigatus isolates recovered from clinical samples in dutch hospitals the prevalence of azole resistance varied between 0.8% and 9.4%. the tr/l98h resistance mechanism probably develops in our environment, as azoles are frequently used for crop protection and material preservation. i ...201222748367
transcriptomic and proteomic analyses of the aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter.aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. to survive in the human body, a. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. recent research suggests that the ability of a. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. however, molecular mechanisms of a. fumigatus hypoxia adaptation are poorly understood. thus, to better understand how a ...201222309491
current understanding of ptx3 protective activity on aspergillus fumigatus infection.infection caused by aspergillus fumigatus remains a major therapeutic challenge in immunocompromised individuals. innate immunity represents the first line of defense against pathogens. in the last 20 years, several proteins belonging to this arm of the immune system have been characterized as being endowed with antifungal activity. among these, the prototype long pentraxin ptx3 has been identified as a non-redundant protective factor against infections caused by a. fumigatus. a number of releva ...201222309253
a novel dehydrin-like protein from aspergillus fumigatus regulates freezing tolerance.we recently reported on dpra and dprb, dehydrin-like proteins involved in the protection against oxidative, osmotic and ph stress in aspergillus fumigatus. a third dehydrin-like gene, dprc, was detected in the genome of the filamentous fungus and repressed during conidial germination. the deletion mutant was impaired in freezing tolerance. the dprc-mediated response was dependent on the saka map kinase pathway, and accordingly, saka phosphorylation was induced by cold shock. when fused to egfp, ...201222306917
trichostatin a abrogates airway constriction, but not inflammation, in murine and human asthma models.histone deacetylase (hdac) inhibitors may offer novel approaches in the treatment of asthma. we postulate that trichostatin a (tsa), a class 1 and 2 inhibitor of hdac, inhibits airway hyperresponsiveness in antigen-challenged mice. mice were sensitized and challenged with aspergillus fumigatus antigen (af) and treated with tsa, dexamethasone, or vehicle. lung resistance (r(l)) and dynamic compliance were measured, and bronchial alveolar lavage fluid (balf) was analyzed for numbers of leukocytes ...201222298527
[triple fungal infection in a patient with liver cirrhosis].the prevalence of invasive mycoses is increasing, especially among patients who are immunocompromised or hospitalized with serious underlying diseases. such infections are associated with a high morbidity and significant mortality, requiring early diagnosis and appropriate treatment but also an optimal prophylaxis in patients with high risk factors. we report a case of triple fungal infection including an invasive pulmonary aspergillosis by aspergillus fumigatus, a candidemia by candida albicans ...201222294141
fetuin a, a serum component, promotes growth and biofilm formation by aspergillus fumigatus.aspergillus fumigatus is an all-important pathogenic fungus and is known for its angiotropism. when it invades human organs, a. fumigatus makes direct contact with blood and its components by causing inflammation and invading vascular structures. to learn the effect of its contact with blood on the development of infection, we examined the effect of serum on a. fumigatus growth. in dulbecco's modified eagle's medium containing 10% fetal bovine serum, hyphal tip growth was accelerated, forming a ...201222293034
nce102 homologue in aspergillus fumigatus is required for normal sporulation, not hyphal growth or pathogenesis.in saccharomyces cerevisiae, nce102 encodes a 173 amino acid transmembrane protein, which acts as a key player in eisosome assembly and plasma membrane organization. here, we describe the characterization of nce102 homologue in the human pathogen, aspergillus fumigatus. our results demonstrated that afunce102 is continuously expressed during fungal growth. in addition, microscopic examination of an afunce102-gfp-expressing transformant confirmed the localization of the fusion protein to the endo ...201222289033
duality of liver and kidney lesions after systemic infection of immunosuppressed and immunocompetent mice with aspergillus fumigatus.invasive aspergillosis is a life-threatening disease mainly caused by aspergillus fumigatus. patients at risk are generally immunocompromised and lungs are assumed to provide the primary site for infection and invasive disease manifestation. contrarily, visceral organ involvement appears to result from a subsequent hematogenous spread. to compare the kinetics of dissemination within deep organs in immunosuppressed vs. immunocompetent mice, we used a bioluminescent a. fumigatus strain in an intra ...201222286702
surface display of gaussia princeps luciferase allows sensitive fungal pathogen detection during cutaneous aspergillosis.non-invasive imaging techniques in microbial disease models have delivered valuable insights in the intimate pathogen-host interplay during infection. here we describe evaluation and validation of a transgenic bioluminescence reporter strain of the human-pathogenic mold aspergillus fumigatus, one of the main fungal pathogens affecting immunocompromised individuals. expression and surface display of the gaussia princeps luciferase allowed sensitive and rapid detection of luminescence emitted from ...201222286700
shedding natural light on fungal infections.bioluminescence imaging allows the visualization of the temporal and spatial progression of biological phenomena, in particular infection, by non-invasive methods in vivo. this nature-borrowed technology has been successfully used to monitor bacterial infections but recent studies have also succeeded in tracking fungal infections such as those caused by the two major opportunistic fungal pathogens candida albicans and aspergillus fumigatus. the findings of donat and collaborators published in th ...201222286695
functional analysis is a paramount prerequisite for understanding the in vitro interaction of human natural killer cells with aspergillus fumigatus. 201222279122
hypersensitivity testing for aspergillus fumigatus ige is significantly more sensitive than testing for aspergillus niger ige.we sought to determine if sufficient redundancy exists between specific ige testing for aspergillus fumigatus and aspergillus niger to eliminate one of the assays in determining aspergillus hypersensitivity. we reviewed regional laboratory results comparing a fumigatus-specific ige with a niger-specific ige using the pharmacia unicap system (pharmacia, kalamazoo, mi). by using the fisher exact test as an index of concordance among paired results, we showed a significant difference between 109 pa ...201222261444
small surfactant-like peptides can drive soluble proteins into active aggregates.inactive protein inclusion bodies occur commonly in escherichia coli (e. coli) cells expressing heterologous proteins. previously several independent groups have found that active protein aggregates or pseudo inclusion bodies can be induced by a fusion partner such as a cellulose binding domain from clostridium cellulovorans (cbdclos) when expressed in e. coli. more recently we further showed that a short amphipathic helical octadecapeptide 18a (ewlkafyekvleklkelf) and a short beta structure pep ...201222251949
interlaboratory comparison of pcr-based identification of candida and aspergillus dna in spiked blood samples.despite pcr per se being a powerful and sensitive technique, regarding the detection of fungi in patients' blood, no consensus for a standardised pcr protocol yet exists. to complement other ongoing or accomplished studies which tackle this problem, the german reference center for systemic mycoses conducted an interlaboratory comparison starting with blood samples spiked with fungal cell elements. altogether, six laboratories using in-house pcr-protocols from germany and austria participated in ...201222248125
outbreak of invasive aspergillosis after major heart surgery caused by spores in the air of the intensive care unit.outbreaks of invasive aspergillosis (ia) are believed to be caused by airborne aspergillus conidia. few studies have established a correlation between high levels of aspergillus fumigatus conidia and the appearance of new cases of ia or have demonstrated matching genotypes between clinical isolates and those from the environment.201222247307
resistin-like molecule-α regulates il-13-induced chemokine production but not allergen-induced airway responses.resistin-like molecule α (relm-α) is one of the most up-regulated gene products in allergen- and parasite-associated th2 responses. localized to alternatively activated macrophages, relm-α was shown to exert an anti-inflammatory effect in parasite-induced th2 responses, but its role in experimental asthma remains unexplored. here, we analyzed the cellular source, the il-4 receptors required to stimulate relm-α production, and the role of relm-α after experimental asthma induction by il-4, il-13, ...201222246861
trivalent ultrashort lipopeptides are potent ph dependent antifungal agents.the activity of antimicrobial peptides (amps) that contain a large proportion of histidine residues (pk(a) ∼ 6) depends on the physiological ph environment. advantages of these amps include high activity in slightly acidic areas of the human body and relatively low toxicity in other areas. also, many amps are highly active in a multivalent form, but this often increases toxicity. here we designed ph dependent amphiphilic compounds consisting of multiple ultrashort histidine lipopeptides on a tri ...201222243686
prophylactic efficacy of single dose pulmonary administration of amphotericin b inhalation powder in a guinea pig model of invasive pulmonary aspergillosis.amphotericin b inhalation powder (abip) is a novel dry-powder amphotericin b formulation that is directly delivered to the lung, resulting in elevated lung tissue drug concentrations of this polyene. we evaluated the prophylactic efficacy of single dose administration of abip in a guinea pig model of invasive pulmonary aspergillosis.201222240402
ctbt (7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine) producing ros affects growth and viability of filamentous fungi.ctbt (7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine) causes intracellular superoxide production and oxidative stress and enhances the susceptibility of saccharomyces cerevisiae, candida albicans, and c. glabrata cells to cycloheximide, 5-fluorocytosine, and azole antimycotic drugs. here, we demonstrate the antifungal activity of ctbt against 14 tested filamentous fungi. ctbt prevented spore germination and mycelial proliferation of aspergillus niger and the pathogenic aspergillus fumigatus. the a ...201222212016
antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment.antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. in vitro susceptibility testing is often used to select agents with likely activity for a given infection, but perhaps its most important use is in identifying agents that will not work, i.e., to detect resistance. standardized methods for reliable in vitro antifungal susceptibility testing are now available from the clinical and laboratory standards institute ...201222196207
invasive fungal infections after renal transplantation.invasive fungal infection (ifi) is a leading cause of infection-related mortality among kidney allograft recipients.201225013619
ras-mediated signal transduction and virulence in human pathogenic fungi.signal transduction pathways regulating growth and stress responses are areas of significant study in the effort to delineate pathogenic mechanisms of fungi. in-depth knowledge of signal transduction events deepens our understanding of how a fungal pathogen is able to sense changes in the environment and respond accordingly by modulation of gene expression and re-organization of cellular activities to optimize fitness. members of the ras protein family are important regulators of growth and diff ...201224855584
fulminant antiphospholipid antibody syndrome complicated by aspergillus tracheobronchitis.aspergillus fumigatus is a filamentous mold that causes infections in patients who are inmmunocompromised. we report a case of aspergillus tracheobronchitis in fulminant systemic lupus erythematosus case. diagnosis with more invasive diagnostic procedures & aggressive antifungal therapy is indicated at early stage.201224371751
early aspergillus pacemaker pocket infection: case and review.we report the first case to our knowledge of an early pacemaker pocket infection due to aspergillus fumigatus. several cases of late pacemaker pocket infection by aspergillus have been reported, but it remains exceedingly rare. recognition of aspergillus infection as a potential early or late complication of placement of pacemakers or implantable cardioverter defibrillator devices may help clinicians diagnose and treat future cases of this potentially devastating infection.201224371732
allergic bronchopulmonary mycosis due to alternaria: case report and review.while allergic bronchopulmonary aspergillosis and mycosis are well recognised, no cases have been described related to alternaria spp. alternaria is a common sensitising fungus in asthmatics and related to thunderstorm asthma. we report a case of an asthmatic who presented with worsening asthma control, mild eosinophilia on high dose inhaled corticosteroids (800 μg/day), a total ige of 3800 kiu/l, an alternaria-specific ige of 21.3 kua/l and positive skin prick test, negative specific ige and sk ...201224371728
aspergillus osteomyelitis of the lumbar spine complicated with orbital apex syndrome: a potential role of the batson's plexus in disease propagation.we report a rare case of orbital apex syndrome following epidural steroid injections of the lumbar spine in an immunocompetent individual with osteomyelitis and discitis caused by aspergillus fumigatus. we suspect that the craniospinal venous system, also known as the batson's plexus, was the main route for steroid-facilitated disease propagation from the spine to intracranial structures.201224371725
the prevalence of positive fungal cultures in patients with chronic rhinosinusitis in a high altitude region of iran.there are suspended fungal spores in the air and in the nasal mucosa of adults, especially in areas with a humid climate. several studies have revealed the role of fungi in the pathogenesis of chronic rhinosinusitis (crs) in recent years but it is a topic of controversy, especially in regions with low humidity. the aim of this study was to evaluate the prevalence of fungal species in intraoperative specimens from patients who underwent functional endoscopic sinus surgery (fess) for crs in hamada ...201224303382
candida albicans: a model organism for studying fungal pathogens.candida albicans is an opportunistic human fungal pathogen that causes candidiasis. as healthcare has been improved worldwide, the number of immunocompromised patients has been increased to a greater extent and they are highly susceptible to various pathogenic microbes and c. albicans has been prominent among the fungal pathogens. the complete genome sequence of this pathogen is now available and has been extremely useful for the identification of repertoire of genes present in this pathogen. th ...201223762753
immune responses in cystic fibrosis: are they intrinsically defective?cystic fibrosis (cf), the most common lethal single-gene disorder affecting northern europeans and north americans, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (cftr) gene. cftr is a chloride channel and a regulator of other ion channels, and many aspects of the cf phenotype are directly related to ion channel abnormalities attributable to cftr mutation. lung disease is the most common limitation to the quantity and quality of life for patients with cf. one ...201222403802
genome mining reveals the presence of a conserved gene cluster for the biosynthesis of ergot alkaloid precursors in the fungal family arthrodermataceae.genome sequence analysis of different fungi of the family arthrodermataceae revealed the presence of a gene cluster consisting of five genes with high sequence similarity to those involved in the early common steps of ergot alkaloid biosynthesis in aspergillus fumigatus and claviceps purpurea. to provide evidence that this cluster is involved in ergot alkaloid biosynthesis, the gene arb_04646 of the fungus arthroderma benhamiae was cloned into pqe60 and expressed in escherichia coli. enzyme assa ...201222403186
triazole fungicides can induce cross-resistance to medical triazoles in aspergillus fumigatus.azoles play an important role in the management of aspergillus diseases. azole resistance is an emerging global problem in aspergillus fumigatus, and may develop through patient therapy. in addition, an environmental route of resistance development has been suggested through exposure to 14α-demethylase inhibitors (dmis). the main resistance mechanism associated with this putative fungicide-driven route is a combination of alterations in the cyp51a-gene (tr(34)/l98h). we investigated if tr(34)/l9 ...201222396740
role of nod2 in regulating the immune response to aspergillus fumigatus.the nucleotide-binding oligomerization domain-2 (nod2) is a type of intracellular receptor recognizing the cell wall molecules of bacteria and inducing the innate immune response. its role in defense against fungal infection remains uncertain. we thus investigated the role of the nod2/rip2 pathway in host responses to aspergillus fumigatus (af) in raw264.7 cells.201222395788
neutrophils mediate maturation and efflux of lung dendritic cells in response to aspergillus fumigatus germ tubes.invasive aspergillosis is a life-threatening complication of neutrophil deficiency or dysfunction. neutropenia has previously been associated with enhanced influx of cd11b-expressing conventional dendritic cells to the lungs in response to aspergillus species, but whether neutrophils directly modulate the function of dendritic cells in this infection is not known. we hypothesized that, in the setting of intrapulmonary challenge with aspergillus, neutrophils promote the maturation and traffic of ...201222392929
the composition of the culture medium influences the β-1,3-glucan metabolism of aspergillus fumigatus and the antifungal activity of inhibitors of β-1,3-glucan synthesis.in vitro testing of aspergillus fumigatus susceptibility to echinocandins has always been a challenge. using a simple and quick colorimetric method to analyze the activity of inhibitors of β-1,3-glucan synthesis, we found that the composition of the culture medium significantly influences glucan synthesis and consequently the antifungal properties of inhibitors of β-1,3-glucan synthesis when they are tested alone or in combination with chitin synthase inhibitors.201222391552
host immune defense against aspergillus fumigatus: insight from experimental systemic (disseminated) infection.model of systemic aspergillus fumigatus infection induced by intravenous application of conidia is suitable for studying important aspects of invasive aspergillosis including relationship between infection and mortality, dissemination of infection and immune mechanisms involved in host resistance to this fungus. use of this model allows the investigation of both innate and adaptive immune response characteristics in resistant/susceptible host, and investigating the contribution of genetic backgr ...201222388638
the performance of real-time pcr, galactomannan, and fungal culture in the diagnosis of invasive aspergillosis in ventilated patients with chronic obstructive pulmonary disease (copd).emerging reports have associated chronic pulmonary obstructive disease (copd) with invasive aspergillosis (ia), particularly in patients treated with mechanical ventilation and/or corticosteroids. this is a multicentre study in which copd patients demonstrating a new lung infiltrate while being mechanically ventilated were prospectively evaluated for the presence of ia. from the 47 patients studied, aspergillus fumigatus was recovered in culture in two patients (4.2%). while serum galactomannan ...201222382738
antimicrobial polyacetylenes from panax ginseng hairy root culture.two new polyacetylenes, 1-hydroxydihydropanaxacol (3) and 17-hydroxypanaxacol (4), were isolated from panax ginseng hairy root culture, along with dihydropanaxacol (1), panaxacol (2) and ginsenoyne d (5). highly hydroxylated compounds 1-4 were isolated from the medium and compound 5, which was a biosynthetic precursor of compound 1, was isolated from the roots. compounds 1-4 showed antimicrobial activity against staphylococcus aureus, bacillus subtilis, cryptococcus neoformans and aspergillus fu ...201222382419
voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization.rationale and objectives. severe asthma with fungal sensitization (safs) and allergic bronchopulmonary aspergillosis (abpa) are progressive allergic fungal lung diseases whose effective treatment remains to be established. current treatment with itraconazole is associated with a 40% failure rate and adverse events (aes). we assessed the effect of voriconazole or posaconazole as second- and third-line therapies. methods. we conducted a retrospective review of adult asthmatic patients with either ...201222380765
aspergillus endocarditis: a case of near complete left ventricular outflow obstruction.a 60-year old woman presented with dyspnoea and fatigue. she was frail and cachectic (bmi 17.5) with a pancytopenia. previously she had received chemotherapy for chronic lymphatic leukaemia. she relapsed one year ago necessitating a reduced intensity conditioning allogeneic haematopoietic cell transplantation. subsequently, graft versus host disease required high-dose immunosuppressants. computerized tomography on admission showed bilateral lung nodules and a suspicious cardiac mass. bronchial b ...201222374293
gliotoxin contamination in and pre- and postfermented corn, sorghum and wet brewer's grains silage in sao paulo and rio de janeiro state, brazil.the aim of this study was to determine total fungal counts and the relative density of aspergillus fumigatus and related species in silage samples intended for bovines before and after fermentation as well as to monitor the natural occurrence of gliotoxin in silage samples (pre- and postfermentation).201222372472
dige enables the detection of a putative serum biomarker of fungal origin in a mouse model of invasive aspergillosis.invasive aspergillosis (ia) is a major threat for immunocompromised patients. diagnostic difficulties often delay specific treatment initiation, which increases mortality. finding new biomarkers to improve and speed accurate diagnosis is thus vital. to investigate the ability of proteomic methods for discovering new biomarkers of ia, we used a dige approach to perform a proteomic analysis on both bronchoalveolar lavages (bal) and sera at different time-points of infection in a mouse model of inv ...201222370163
developments in novel breath tests for bacterial and fungal pulmonary infection.breath testing has developed over the last 20 years. new techniques that can identify fingerprints for specific diseases and specific markers of respiratory pathogens have been applied to breath analysis. this review discusses the recent advances in breath analysis for the diagnosis of bacterial and fungal lower respiratory tract infections.201222366996
antibody specific to thioredoxin reductase as a new biomarker for serodiagnosis of invasive aspergillosis in non-neutropenic patients.invasive aspergillosis (ia) is an important cause of mortality in critically ill patients, but the diagnosis is difficult as clinical and radiological signs are neither sensitive nor specific. serum galactomannan (gm) is a useful marker for ia, but exhibits low sensitivity in non-neutropenic patients. in our previous work, strong antibody reactivity to thioredoxin reductase of aspergillus fumigatus was found in non-neutropenic ia patients.201222366166
an unusual case of non-disseminated bladder aspergillosis in a setting of transitional cell carcinoma.a bladder infection of aspergillus with no evidence of dissemination is rare. we present a case of aspergillus infection with transitional cell carcinoma of the urinary bladder without any evidence of systemic involvement. a 65-year-old male diabetic whose main complaints were intermittent painful haematuria and nocturia had undergone nephroureterectomy a year and a half back for transitional cell carcinoma of right renal pelvis. cystoscopy revealed bladder mucosa having fixed broad tumour with ...201222361774
secretome of human bronchial epithelial cells in response to the fungal pathogen aspergillus fumigatus analyzed by differential in-gel electrophoresis.for years, the analysis of innate responses to the major mold pathogen aspergillus fumigatus has been restricted to specialized cells, such as professional phagocytes. more recently, the contribution of the airway epithelial barrier has been assessed and studies have shown that it was able to sense and react to the aspergillus infection, for example, by producing cytokines.201222357658
sensing of mammalian il-17a regulates fungal adaptation and virulence.infections by opportunistic fungi have traditionally been viewed as the gross result of a pathogenic automatism, which makes a weakened host more vulnerable to microbial insults. however, fungal sensing of a host's immune environment might render this process more elaborate than previously appreciated. here we show that interleukin (il)-17a binds fungal cells, thus tackling both sides of the host-pathogen interaction in experimental settings of host colonization and/or chronic infection. global ...201222353714
clinical characteristics and prognosis of chronic pulmonary aspergillosis.the details of the clinical characteristics of patients with chronic pulmonary aspergillosis (cpa) have not been fully understood.201222349065
total synthesis and structure-activity relationships of new echinocandin-like antifungal cyclolipohexapeptides.a series of new echinocandin-like cyclolipohexapeptides were designed and total synthesized via solution phase [3 + 3]-segment coupling strategy with an attempt to improve antifungal activity. the designed compounds showed potent antifungal activities with broad spectrum. in particular, 11 compounds (i.e. 28a-e, 28g, 28i-j, 29a, 29c and 29e) showed better in vitro antifungal activities against candida albicans or aspergillus fumigatus than caspofungin. moreover, the synthesized compounds provide ...201222348827
iron - a key nexus in the virulence of aspergillus fumigatus.iron is an essential but, in excess, toxic nutrient. therefore, fungi evolved fine-tuned mechanisms for uptake and storage of iron, such as the production of siderophores (low-molecular mass iron-specific chelators). in aspergillus fumigatus, iron starvation causes extensive transcriptional remodeling involving two central transcription factors, which are interconnected in a negative transcriptional feed-back loop: the gata-factor srea and the bzip-factor hapx. during iron sufficiency, srea repr ...201222347220
molecular characterization of the putative transcription factor seba involved in virulence in aspergillus fumigatus.aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. nutrient sensing and acquisition mechanisms, as well as the capability to cope with different stressing conditions, are essential for a. fumigatus virulence and survival in the mammalian host. this study characterized the a. fumigatus seba transcription factor, which is the putative homologue of the factor encoded by trichoderma atroviride seb1. the δseba mutant demonstrated reduced growth in the presence of paraqua ...201222345349
2,5-diketopiperazines from the marine-derived fungus aspergillus fumigatus yk-7.five new diketopiperazines, prenylcyclotryprostatin b (1), 20-hydroxycyclotryprostatin b (2), 9-hydroxyfumitremorgin c (3), 6-hydroxytryprostatin b (4), and spirogliotoxin (5), were isolated from the marine-derived fungus aspergillus fumigatus yk-7, along with nine known compounds, 6-14. their structures were elucidated by spectroscopic methods, and their antiproliferative effects on human leukemic monocyte lymphoma u937 and human prostate cancer pc-3 cell lines were assessed in vitro. compounds ...201222344914
nonribosomal peptide synthetase genes pesl and pes1 are essential for fumigaclavine c production in aspergillus fumigatus.the identity of metabolites encoded by the majority of nonribosomal peptide synthetases in the opportunistic pathogen, aspergillus fumigatus, remains outstanding. we found that the nonribosomal peptide (nrp) synthetases pesl and pes1 were essential for fumigaclavine c biosynthesis, the end product of the complex ergot alkaloid (ea) pathway in a. fumigatus. deletion of either pesl (δpesl) or pes1 (δpes1) resulted in complete loss of fumigaclavine c biosynthesis, relatively increased production of ...201222344643
risk factors for mycobacterium abscessus infection in cystic fibrosis patients; a case-control study.mycobacterium abscessus is a nontuberculous mycobacterium that is increasingly recognized as an opportunistic pathogen in cystic fibrosis (cf) patients. factors that predispose cf patients to infection by this environmental bacterium remain unknown. in a case-control study of 22 cf patients with m. abscessus infection and 22 cf controls, we investigated risk factors for mab infection as well as the positioning of mab infection in relation to the other pathogens infecting cf patients. no clear ri ...201222342403
[aspergillosis. clinical forms and treatment].invasive aspergillosis, chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis are the clinical forms of aspergillosis. although there is a great number of aspergillus species, aspergillus fumigatus-complex is the more frequent aetiological agent, regardless of clinical form or baseline condition. the increase in immunosuppressive agents and the higher use of corticosteroids in chronic obstructive pulmonary disease have led to aspergillosis becoming more prominent in recent ...201222341751
characterization of a thermostable β-glucosidase from aspergillus fumigatus z5, and its functional expression in pichia pastoris x33.recently, the increased demand of energy has strongly stimulated the research on the conversion of lignocellulosic biomass into reducing sugars for the subsequent production, and β-glucosidases have been the focus because of their important roles in a variety fundamental biological processes and the synthesis of useful β-glucosides. although the β-glucosidases of different sources have been investigated, the amount of β-glucosidases are insufficient for effective conversion of cellulose. the goa ...201222340848
structural insight into the unique substrate binding mechanism and flavin redox state of udp-galactopyranose mutase from aspergillus fumigatus.udp-galactopyranose mutase (ugm) is a flavin-containing enzyme that catalyzes the reversible conversion of udp-galactopyranose (udp-galp) to udp-galactofuranose (udp-galf). as in prokaryotic ugms, the flavin needs to be reduced for the enzyme to be active. here we present the first eukaryotic ugm structures from aspergillus fumigatus (afugm). the structures are of ugm alone, with the substrate udp-galp and with the inhibitor udp. additionally, we report the structures of afugm bound to substrate ...201222334662
epidemiological cutoff values for azoles and aspergillus fumigatus based on a novel mathematical approach incorporating cyp51a sequence analysis.epidemiological cutoff values (ecv) are commonly used to separate wild-type isolates from isolates with reduced susceptibility to antifungal drugs, thus setting the foundation for establishing clinical breakpoints for aspergillus fumigatus. however, ecvs are usually determined by eye, a method which lacks objectivity, sensitivity, and statistical robustness and may be difficult, in particular, for extended and complex mic distributions. we therefore describe and evaluate a statistical method of ...201222330922
keratomycosis caused by aspergillus viridinutans: an aspergillus fumigatus-resembling mold presenting distinct clinical and antifungal susceptibility patterns.we report here a case of fungal keratitis caused by aspergillus viridinutans, a member of the genus which was found to have clinical and antifungal susceptibility characteristics distinct from the species it most closely resembles, aspergillus fumigatus. a 26-year-old woman presented with contact lens-associated keratitis, the etiologic agent of which was initially slow growing and found to be resistant to amphotericin b and voriconazole. therapeutic keratoplasty was performed and an isolate fro ...201222329455
a nebulized intra-tracheal rat model of invasive pulmonary aspergillosis.animal models are particularly useful for the study of many infectious diseases, including those caused by fungi. invasive pulmonary aspergillosis is most frequently studied in mouse models. we present here an animal model of this disease based on undernourished immunocompromised rats infected with aspergillus fumigatus spores by intra-tracheal nebulisation.201222328399
embryonated chicken eggs as alternative infection model for pathogenic fungi.embryonated eggs have been used as infection models for decades in virology and bacteriology. however, they can also be used as an attractive alternative infection model for studying fungal pathogenesis. here, we discuss some general aspects which need to be considered when working with embryonated eggs as infection models. furthermore, we provide detailed protocols and technical tips for infection of embryonated eggs with aspergillus fumigatus and candida albicans via the chorioallantois membra ...201222328397
simple assays for measuring innate interactions with fungi.in recent decades, there has been a steady rise in immunocompromised populations and consequently a dramatic increase in the clinical relevance of normally non-pathogenic and commensal fungi such as aspergillus fumigatus and candida albicans. understanding how these fungi interact with the host immune system is important for the development of immunotherapeutic approaches. here, we describe a number of methods which have been developed to investigate the interactions of fungi with host leukocyte ...201222328383
targeted gene deletion in aspergillus fumigatus using the hygromycin-resistance split-marker approach.the construction of a fungal strain that lacks a specific gene product is often accomplished by replacing the gene of interest with a selection marker using site-specific recombination. transformation of aspergillus fumigatus, like many related fungal species, must overcome two major obstacles. first, the cell wall limits the entry of exogenous dna, and second, a high rate of nonhomologous recombination leads to random ectopic integration of the marker. here, we describe an experimental strategy ...201222328371
gene disruption in aspergillus fumigatus using a pcr-based strategy and in vivo recombination in yeast.aspergillus fumigatus is a ubiquitous, filamentous fungal saprophyte and is the causative agent of the vast majority of aspergillosis in that invasive aspergillosis is the life-threatening form of infection by this fungus. the study of gene function using null mutants in this organism can be achieved through dna-mediated transformation with an engineered deletion cassette containing about 2 kb of the 5'- and 3'-flanking region of the target gene and a selectable marker. here, we describe the use ...201222328370
production of thermophilic endo-β-1,4-xylanases by aspergillus fumigatus fbspe-05 using agro-industrial by-products.in the present paper, endo-β-1,4-xylanase production by aspergillus fumigatus was evaluated in solid-state fermentation using low-cost substrates such as sugarcane bagasse (scb), brewer's spent grain (bsg), and wheat bran (wb). the partial characterization of the crude enzyme was also performed. in the experimental conditions, the highest levels of endo-β-1,4-xylanase production by a. fumigatus fbspe-05 occurred within 8 days incubation when using scb/liquid medium at 1:2 ratio (219.5 u g(-1)) a ...201222328248
persistence versus escape: aspergillus terreus and aspergillus fumigatus employ different strategies during interactions with macrophages.invasive bronchopulmonary aspergillosis (ibpa) is a life-threatening disease in immunocompromised patients. although aspergillus terreus is frequently found in the environment, a. fumigatus is by far the main cause of ibpa. however, once a. terreus establishes infection in the host, disease is as fatal as a. fumigatus infections. thus, we hypothesized that the initial steps of disease establishment might be fundamentally different between these two species. since alveolar macrophages represent o ...201222319619
trypacidin, a spore-borne toxin from aspergillus fumigatus, is cytotoxic to lung cells.inhalation of aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. a. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. we found that spores of a. fumigatus contain five main compounds, tryptoquivaline f, fumiquinazoline c, questin, monomethylsulochrin and trypacidin. fractionation of culture extracts using rp-hplc and lc-ms showed that sample ...201222319557
species-specific recognition of aspergillus fumigatus by toll-like receptor 1 and toll-like receptor 6.aspergillus fumigatus causes invasive aspergillosis, a potentially fatal infection in oncohematological patients. innate immune detection of a. fumigatus involves toll-like receptor (tlr) 4 and tlr2, which forms a heterodimer with either tlr1 or tlr6. the role of those coreceptors in aspergillus sensing is unknown.201222315281
expression turnover profiling to monitor the antifungal activities of amphotericin b, voriconazole, and micafungin against aspergillus fumigatus.eight highly expressed candidate genes were selected for mrna profiling to monitor the transcriptome kinetics of aspergillus fumigatus strains exposed to antifungal drugs as potential biomarkers of live cells to assess treatment efficacy. mycelia were treated with fungicidal drugs amphotericin b and voriconazole, as well as the fungistatic drug micafungin. transcription was monitored at 0, 4, 8, and 24 h posttreatment. the expression turnover profile provides a possible tool to assess antifungal ...201222314535
assessment of aspergillus fumigatus in guinea pig bronchoalveolar lavages and pulmonary tissue by culture and realtime polymerase chain reaction studies.in this study we pursued a diagnostic target in aspergillus fumigatus (af) by using qualitative realtime pcr combined with proprietary dna primers and a hydrolysis probe specific for this fungal target. qualitative realtime pcr is a diagnostic tool that utilizes realtime pcr technology and detects the presence or absence target specific dna within a predetermined detection range. respiratory tissue and fluids from experimentally infected guinea pigs were tested by extracting dna from the samples ...201222312282
isolation of filamentous fungi from sputum in asthma is associated with reduced post-bronchodilator fev1.fungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. the range of fungi that may colonize the airways in asthma is unknown.201222515394
germination of aspergillus fumigatus inside avian respiratory macrophages is associated with cytotoxicity.although aspergillosis is one of the most common diseases in captive birds, the pathogenesis of avian aspergillosis is poorly known. we studied the role of avian respiratory macrophages as a first line of defense against avian aspergillosis. the phagocytic and killing capacities of avian respiratory macrophages were evaluated using pigeon respiratory macrophages that were inoculated with aspergillus fumigatus conidia. on average, 25% of macrophage-associated conidia were phagocytosed after one h ...201222515231
transcriptional and proteomic analysis of the aspergillus fumigatus δprtt protease-deficient mutant.aspergillus fumigatus is the most common opportunistic mold pathogen of humans, infecting immunocompromised patients. the fungus invades the lungs and other organs, causing severe damage. penetration of the pulmonary epithelium is a key step in the infectious process. a. fumigatus produces extracellular proteases to degrade the host structural barriers. the a. fumigatus transcription factor prtt controls the expression of multiple secreted proteases. prtt shows similarity to the fungal gal4-type ...201222514608
identification of novel genes conferring altered azole susceptibility in aspergillus fumigatus.azoles are currently the mainstay of antifungal treatment both in agricultural and in clinical settings. although the target site of azole action is well studied, the basis of azole resistance and the ultimate mode of action of the drug in fungi are poorly understood. to gain a deeper insight into these aspects of azole action, restriction-mediated plasmid integration (remi) was used to create azole sensitive and resistant strains of the clinically important fungus aspergillus fumigatus. four az ...201222509997
towards the crystal structure elucidation of eukaryotic udp-galactopyranose mutase.udp-galactopyranose mutase (ugm) catalyzes the interconversion of udp-galactopyranose and udp-galactofuranose. eukaryotic ugms from aspergillus fumigatus and leishmania major have been purified to homogeneity by means of ni(2+)-affinity chromatography and crystallized. eukaryotic ugm structure elucidation was not straightforward owing to high pseudo-symmetry, twinning and very low anomalous signal. phasing to 2.8 å resolution using sad was successful for l. major ugm. however, the maps could onl ...201222505419
cytotoxicity and antimicrobial activity of the methanol extract and compounds from polygonum limbatum.the present study was designed to investigate the antimicrobial activity and the cytotoxicity of the methanol extract (pla) as well as fractions (pla1-4) and compounds [cardamomin (1), (±)-polygohomoisoflavanone (2), (s)-(-)-pinostrobin (3), 2',4'-dihydroxy-3',6'-dimethoxychalcone (4), (2s)-(-)-5-hydroxy-6,7-dimethoxyflavanone (5), and (2s)-(-)-5,7-dimethoxyflavanone (6)] obtained from leaves of polygonum limbatum. the microbroth dilution was used to determine the minimal inhibitory concentratio ...201222495442
a low-molecular-mass aspartic protease inhibitor from a novel penicillium sp.: implications in combating fungal infections.a low-molecular-mass aspartic protease inhibitor was isolated from a novel penicillium sp. the inhibitor was purified to homogeneity, as shown by reversed-phase hplc and sds-page. the m(r) of the inhibitor was 1585 and the amino acid composition showed the presence of d, d, d, e, a, k, l, y, h, i and w residues. the steady-state kinetic interactions of aspergillus saitoi aspartic protease with the inhibitor revealed the reversible, competitive, time-dependent tight-binding nature of the inhibito ...201222493301
genome-based cluster deletion reveals an endocrocin biosynthetic pathway in aspergillus fumigatus.endocrocin is a simple anthraquinone frequently identified in extracts of numerous fungi. several biosynthetic schemes for endocrocin synthesis have been hypothesized, but to date, no dedicated secondary metabolite gene cluster that produces this polyketide as its major metabolite has been identified. here we describe our biosynthetic and regulatory characterization of the endocrocin gene cluster in aspergillus fumigatus. this is the first report of this anthraquinone in this species. the biosyn ...201222492455
e-cadherin mediates adhesion and endocytosis of aspergillus fumigatus blastospores in human epithelial cells.aspergillus fumigatus (a. fumigatus) is a ubiquitous saprophytic fungus responsible for the majority of invasive mold infections in patients undergoing chemotherapy, organ transplantation or with persistent neutropenia. this study aimed to determine the role of e-cadherin for adhesion and endocytosis of a. fumigatus blastospores in the human epithelial cell line a549.201222490484
vanishing bronchus intermedius syndrome in a pediatric patient with cystic fibrosis after lung transplantation.airway complications occur frequently after lung transplantation. bronchial stenosis is the most frequently encountered complication with the most severe form of that being the vanishing bronchus intermedius syndrome (vbis). this rare disorder has never been reported in the pediatric population. this is the first report of vbis in a pediatric patient, specifically a 16-yr-old male patient with cystic fibrosis whose course was complicated by a lower airway infection with aspergillus fumigatus. th ...201222489792
chronic aspergillus fumigatus exposure upregulates the expression of mucin 5ac in the airways of asthmatic rats.airway mucus hypersecretion is associated with increased morbidity and mortality in patients with asthma. chronic aspergillus fumigatus (a. fumigatus) exposure leads to aggravation of airway inflammation and remodeling, including goblet cell hyperplasia (gch) and mucus hypersecretion in a rat model of asthma. the effects of chronic a. fumigatus exposure on the expression of airway mucin 5ac (muc5ac) are unknown.201222489685
systems biology of fungal infection.elucidation of pathogenicity mechanisms of the most important human-pathogenic fungi, aspergillus fumigatus and candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections. a key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. because of the high level of complexity, it is necessary to describe and understand invasive fungal infecti ...201222485108
recurrent fungal iris granuloma in a 10-year-old child.to report the diagnosis of a case of recurrent iris fungal granuloma presumed to be an iris tuberculoma in a 10-year-old girl.201222480141
characterisation of innate fungal recognition in the lung.the innate recognition of fungi by leukocytes is mediated by pattern recognition receptors (prr), such as dectin-1, and is thought to occur at the cell surface triggering intracellular signalling cascades which lead to the induction of protective host responses. in the lung, this recognition is aided by surfactant which also serves to maintain the balance between inflammation and pulmonary function, although the underlying mechanisms are unknown. here we have explored pulmonary innate recognitio ...201222536422
microcolony imaging of aspergillus fumigatus treated with echinocandins reveals both fungistatic and fungicidal activities.the echinocandins are lipopeptides that can be employed as antifungal drugs that inhibit the synthesis of 1,3-β-glucans within the fungal cell wall. anidulafungin and caspofungin are echinocandins used in the treatment of candida infections and have activity against other fungi including aspergillus fumigatus. the echinocandins are generally considered fungistatic against aspergillus species.201222536390
analyzing disease risks associated with translocations.translocations of species are expected to be used increasingly to counter the undesirable effects of anthropogenic changes to ecosystems, including loss of species. methods to assess the risk of disease associated with translocations have been compiled in a comprehensive manual of disease-risk analysis for movement of domestic animals. we used this manual to devise a qualitative method for assessing the probability of the occurrence of disease in wild animals associated with translocations. we a ...201222533691
proteomic characterization of aspergillus fumigatus treated with an antifungal coumarin for identification of novel target molecules of key pathways.a synthetic coumarin, n,n,n-triethyl-11-(4-methyl-2-oxo-2h-chromen-7-yloxy)-11-oxoundecan-1-aminium bromide (scd-1), having potent activity against pathogenic aspergilli (mic90 15.62 μg/ml), was investigated to identify its molecular targets in the pathogen. the proteome of aspergillus fumigatus was developed after treatment with sublethal doses of compound and analyzed. the results demonstrated 143 differentially expressed proteins on treatment with scd-1. the expression of four proteins, namel ...201222533410
sago pith residue as an alternative cheap substrate for fermentable sugars production.sago pith residue is one of the most abundant lignocellulosic biomass which can serve as an alternative cheap substrate for fermentable sugars production. this residue is the fibrous waste left behind after the starch extraction process and contains significant amounts of starch (58%), cellulose (23%), hemicellulose (9.2%) and lignin (3.9%). the conversion of sago pith residue into fermentable sugars is commonly performed using cellulolytic enzymes or known as cellulases. in this study, crude ce ...201222528646
preclinical evaluation of two 68ga-siderophores as potential radiopharmaceuticals for aspergillus fumigatus infection imaging.invasive pulmonary aspergillosis is mainly caused by aspergillus fumigatus, and is one of the major causes of morbidity and mortality in immunocompromised patients. the mortality associated with invasive pulmonary aspergillosis remains high, mainly due to the difficulties and limitations in diagnosis. we have shown that siderophores can be labelled with (68)ga and can be used for pet imaging of a. fumigatus infection in rats. here we report on the further evaluation of the most promising (68)ga- ...201222526953
development of novel pcr assays to detect azole resistance-mediating mutations of the aspergillus fumigatus cyp51a gene in primary clinical samples from neutropenic patients.the increasing incidence of azole resistance in aspergillus fumigatus causing invasive aspergillosis (ia) in immunocompromised/hematological patients emphasizes the need to improve the detection of resistance-mediating cyp51a gene mutations from primary clinical samples, particularly as the diagnosis of invasive aspergillosis is rarely based on a positive culture yield in this group of patients. we generated primers from the unique sequence of the aspergillus fumigatus cyp51a gene to establish p ...201222526309
immediate hypersensitivity and serum ige antibody responses in patients with dermatophytosis.the association of dermatophytes with atopic patients and improvement in allergic signs with antifungal treatment suggest a possible link between chronic infection and atopy.201222523906
cd4(+) t cell vaccination overcomes defective cross-presentation of fungal antigens in a mouse model of chronic granulomatous disease.aspergillus fumigatus is a model fungal pathogen and a common cause of infection in individuals with the primary immunodeficiency chronic granulomatous disease (cgd). although primarily considered a deficiency of innate immunity, cgd is also linked to dysfunctional t cell reactivity. both cd4(+) and cd8(+) t cells mediate vaccine-induced protection from experimental aspergillosis, but the molecular mechanisms leading to the generation of protective immunity and whether these mechanisms are dysre ...201222523066
the interplay between vacuolar and siderophore-mediated iron storage in aspergillus fumigatus.iron is an essential element for all eukaryotes but its excess has deleterious effects. aspergillus fumigatus produces extracellular siderophores for iron uptake and the intracellular siderophore ferricrocin (fc) for distribution and storage of iron. iron excess has previously been shown to increase the content of ferric fc and the expression of the putative vacuolar iron importer ccca (afua_4g12530), indicating a role of both the vacuole and fc in iron detoxification. in this study, we show tha ...201223151814
enhancement of commercial antifungal agents by kojic acid.natural compounds that pose no significant medical or environmental side effects are potential sources of antifungal agents, either in their nascent form or as structural backbones for more effective derivatives. kojic acid (ka) is one such compound. it is a natural by-product of fungal fermentation commonly employed by food and cosmetic industries. we show that ka greatly lowers minimum inhibitory (mic) or fungicidal (mfc) concentrations of commercial medicinal and agricultural antifungal agent ...201223203038
azole-resistant aspergillus fumigatus due to tr46/y121f/t289a mutation emerging in belgium, july 2012.a new azole resistance mechanism in aspergillus fumigatus consisting of a tr46/y121f/t289a alteration in the cyp51a gene was recently described in the netherlands. strains containing these mutations are associated with invasive infection and therapy failure. this communication describes the first case of fatal invasive aspergillosis caused by tr46/y121f/t289a outside the netherlands, in the neighboring country of belgium, suggesting geographical spread. tr46/y121f/t289a leads to a recognisable p ...201223218390
[the importance of bronchoalveolar lavage sample for galactomannan, 1,3-ß-d-glucan and pcr tests].opportunistic fungal infections are life threatening especially for immunosuppressed patients. early and accurate diagnosis is very important for the prompt initiation of treatment and to reduce unnecessary use of antifungal drugs. in recent years, efforts providing more rapid and more sensitive diagnosis of invasive fungal infections have been increasing. these methods include detection of fungal antigens, specific antibodies, fungal metabolites and dna in the clinical samples. in this case, we ...201223188584
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