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a rare case of aspergillus pericarditis with associated myocardial abscess and echocardiographic response to therapy.myocardial abscess is an extremely rare entity and is often deadly in nature. we present a case of a patient with recent orthotopic liver transplant, on immunosuppression, who presented with cardiac tamponade due to aspergillus fumigatus pericarditis and associated myocardial abscess. the diagnosis was made based on computed tomography imaging, culture of pericardial fluid for aspergillus, and transthoracic echocardiography. the patient received antifungal therapy with clinical improvement and d ...201627009593
high prevalence of clinical and environmental triazole-resistant aspergillus fumigatus in iran: is it a challenging issue?triazole antifungal agents are the mainstay of aspergillosis treatment. as highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. in the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of iran were processed and screened in terms of azole resistance (4 and 1 mg l-1 of itraconazole and voriconazole, respectively), using selective plates. overall, 150 a. fumigat ...201627008655
hypoxia attenuates anti-aspergillus fumigatus immune responses initiated by human dendritic cells.aspergillus fumigatus is an opportunistic mould that causes invasive pulmonary aspergillosis (ipa), a life-threatening infection in immunocompromised patients. during the course of ipa, localised areas of tissue hypoxia occur. bacterial infection models revealed that hypoxic microenvironments modulate the function of host immune cells. however, the influence of hypoxia on anti-fungal immunity has been largely unknown. we evaluated the impact of hypoxia on the human anti-a. fumigatus immune respo ...201627005862
antimicrobial activity of the pygidial gland secretion of three ground beetle species (insecta: coleoptera: carabidae).the antimicrobial properties of the pygidial gland secretions released by the adults of the three ground beetle species, carabus ullrichii, c. coriaceus, and abax parallelepipedus, have been tested. microdilution method was applied for detection of minimal inhibitory concentrations (mics), minimal bactericidal concentrations (mbcs), and minimal fungicidal concentrations (mfcs). additionally, morpho-histology of the pygidial glands is investigated. we have tested 16 laboratory and clinical strain ...201627000261
anti-aspergillus immunoglobulin-g testing in serum of hematopoietic stem cell transplant recipients.pulmonary invasive aspergillosis (ia) is a major clinical problem in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-hsct). acquisition of ia during allo-hsct by inhalation of spores is the rationale for the widespread use of air filtration systems. recent data suggest that activation of fungal growth in already colonized patients is a relevant factor, and a recent study found a positive correlation of serum immunoglobulin responses against purified recombinant asper ...201626998687
the hypoxia-induced dehydrogenase hora is required for coenzyme q10 biosynthesis, azole sensitivity and virulence of aspergillus fumigatus.aspergillus fumigatus is the predominant airborne pathogenic fungus causing invasive aspergillosis in immunocompromised patients. during infection a. fumigatus has to adapt to oxygen-limiting conditions in inflammatory or necrotic tissue. previously, we identified a mitochondrial protein to be highly up-regulated during hypoxic adaptation. here, this protein was found to represent the novel oxidoreductase hora. in saccharomyces cerevisiae a homologue was shown to play a role in biosynthesis of c ...201626991818
bronchiectasis: current concepts in pathogenesis, immunology, and microbiology.bronchiectasis is a disorder of persistent lung inflammation and recurrent infection, defined by a common pathological end point: irreversible bronchial dilatation arrived at through diverse etiologies. this suggests an interplay between immunogenetic susceptibility, immune dysregulation, bacterial infection, and lung damage. the damaged epithelium impairs mucus removal and facilitates bacterial infection with increased cough, sputum production, and airflow obstruction. lung infection is caused ...201626980162
[tslpr/stat5 signaling modulates innate immunity in corneal fibroblasts triggered by aspergillus fumigatus].to study the primary role of tslpr/stat5 signaling in inflammatory responses triggered by aspergillus fumigatus(af) in telomerase-immortalized human stromal fibroblasts (thsf).201626979118
comparison of reflectance confocal microscopy and two-photon second harmonic generation microscopy in fungal keratitis rabbit model ex vivo.fungal keratitis is an infection of the cornea by fungal pathogens. diagnosis methods based on optical microscopy could be beneficial over the conventional microbiology method by allowing rapid and non-invasive examination. reflectance confocal microscopy (rcm) and two-photon second harmonic generation microscopy (tpshgm) have been applied to pre-clinical or clinical studies of fungal keratitis. in this report, rcm and tpshgm were characterized and compared in the imaging of a fungal keratitis r ...201626977371
proteomic profiling of serological responses to aspergillus fumigatus antigens in patients with invasive aspergillosis.aspergillus fumigatus is the species that most commonly causes the opportunistic infection invasive aspergillosis (ia) in patients being treated for hematological malignancies. little is known about the a. fumigatus proteins that trigger the production of aspergillus-specific igg antibodies during the course of ia. to characterize the serological response to a. fumigatus protein antigens, mycelial proteins were separated by 2-d gel electrophoresis. the gels were immunoblotted with sera from pati ...201626974881
detection of a serum siderophore by lc-ms/ms as a potential biomarker of invasive aspergillosis.invasive aspergillosis (ia) is a life-threatening systemic mycosis caused primarily by aspergillus fumigatus. early diagnosis of ia is based, in part, on an immunoassay for circulating fungal cell wall carbohydrate, galactomannan (gm). however, a wide range of sensitivity and specificity rates have been reported for the gm test across various patient populations. to obtain iron in vivo, a. fumigatus secretes the siderophore, n,n',n"-triacetylfusarinine c (tafc) and we hypothesize that tafc may r ...201626974544
isolated orbital aspergillosis in immunocompetent patients: a multicenter study.to report clinicopathologic features, radiologic findings, and treatment outcomes of isolated, orbital aspergillosis.201626973050
functional analysis of the gene controlling hydroxylation of festuclavine in the ergot alkaloid pathway of neosartorya fumigata.bioactive ergot alkaloids produced by several species of fungi are important molecules in agriculture and medicine. much of the ergot alkaloid pathway has been elucidated, but a few steps, including the gene controlling hydroxylation of festuclavine to fumigaclavine b, remain unsolved. festuclavine is a key intermediate in the fumigaclavine branch of the ergot alkaloid pathway of the opportunistic pathogen neosartorya fumigata and also in the dihydrolysergic acid-based ergot alkaloid pathway of ...201626972831
subcellular compartmentalization and trafficking of the biosynthetic machinery for fungal melanin.protection by melanin depends on its subcellular location. although most filamentous fungi synthesize melanin via a polyketide synthase pathway, where and how melanin biosynthesis occurs and how it is deposited as extracellular granules remain elusive. using a forward genetic screen in the pathogen aspergillus fumigatus, we find that mutations in an endosomal sorting nexin abolish melanin cell-wall deposition. we find that all enzymes involved in the early steps of melanin biosynthesis are recru ...201626972005
synthesis and antimicrobial activity of bis-[4-methoxy-3-(6-aryl-7h-[1,2,4]triazolo[3,4-b][1,3,4]-thiadiazin-3-yl)phenyl]methanes and bis-[(triazolo[3,4-b]thiadiazipin-3-yl)phenyl]methanes.a series of novel bis-[4-methoxy-3-(6-aryl-7h-[1,2,4]tria zolo[3,4-b][1,3,4]-thiadiazin-3-yl)phenyl]methanes and bis-[(triazolo[3,4-b]thiadiazipin-3-yl)phenyl]methanes ( 5a-e & 6a-e ) has been synthesized and characterized by ir, (1)h nmr, (13)c nmr, ms and elemental analysis. all the newly synthesized compounds were screened for their antibacterial activity against bacillus subtilis, staphylococcus aureus, klobsinella aerogenes and chromobacteriumviolaceum and antifungal activity against candid ...201626970802
[aspergillus fumigatus mediastinitis in an immunocompetent pediatric patient after heart surgery].postsurgical aspergillosis occurs primarily in immunocompetent patients whose main predisposing factor is the loss of skin and mucosal integrity during surgery. local infection tends to be destructive and refractory to treatment and relapses are common. it is important to consider aspergillosis in the differential diagnosis of slowly progressive and destructive surgical site infections with negative bacterial cultures. we present the case of a child who developed aspergillus fumigatus mediastini ...201626965883
pkc-δ activation in neutrophils promotes fungal clearance.the c-type lectin receptor dectin-1 and the integrin mac-1 have key roles in controlling fungal infection. here, we demonstrate that dectin-1- and mac-1-induced activation of protein kinase cδ in neutrophils, independent of the card9 adaptor, is required for reactive oxygen species production and for intracellular killing upon candida albicans uptake. protein kinase cδ was also required for zymosan-induced cytokine generation in neutrophils. in macrophages, protein kinase cδ deficiency prevented ...201626965632
inhibition of trem-1 and dectin-1 alleviates the severity of fungal keratitis by modulating innate immune responses.to explore the possibility that inhibiting triggering receptor expressed on myeloid cells-1 (trem-1) and dendritic cell-associated c-type lectin-1(dectin-1) could modulate the innate immune response and alleviate the severity of corneal fungal keratitis.201626963514
spacer-free bodipy fluorogens in antimicrobial peptides for direct imaging of fungal infection in human tissue.fluorescent antimicrobial peptides are promising structures for in situ, real-time imaging of fungal infection. here we report a fluorogenic probe to image aspergillus fumigatus directly in human pulmonary tissue. we have developed a fluorogenic trp-bodipy amino acid with a spacer-free c-c linkage between trp and a bodipy fluorogen, which shows remarkable fluorescence enhancement in hydrophobic microenvironments. the incorporation of our fluorogenic amino acid in short antimicrobial peptides doe ...201626956772
distinct roles of myosins in aspergillus fumigatus hyphal growth and pathogenesis.myosins are a family of actin-based motor proteins found in many organisms and are categorized into classes based on their structures. class ii and v myosins are known to be important for critical cellular processes, including cytokinesis, endocytosis, exocytosis, and organelle trafficking, in the model fungi saccharomyces cerevisiae and aspergillus nidulans however, the roles of myosins in the growth and virulence of the pathogen aspergillus fumigatus are unknown. we constructed single- and dou ...201626953327
expression of s100b during the innate immune of corneal epithelium against fungi invasion.to explore the expression of s100b in corneal epithelial cells under aspergillus stimulation both in vivo and in vitro.201626949634
co-regulation of dectin-1 and tlr2 in inflammatory response of human corneal epithelial cells induced by aspergillus fumigates.to investigate the co-regulation of dendritic cell-associated c-type lectin-1 (dectin-1), toll-like receptor 2 (tlr2), and relative chemotactic factors in the telomease-immortalized human corneal epithelial (thce) cells after exposure to aspergillus fumigatus (af) hyphae.201626949633
comparison of the composition and antimicrobial activities of the essential oils of green branches and leaves of egyptian navel orange (citrus sinensis (l.) osbeck var. malesy).the essential oils isolated from the leaves and green branches of the egyptian navel orange trees were analyzed by gc and gc/ms. a total of 33 and 24 compounds were identified from the oils of the leaves and branches accounting for 96.0% and 97.9%, respectively, of the total detected constituents. the major ones were sabinene (36.5; 33.0%), terpinen-4-ol (8.2; 6.2%), δ-3-carene (7.0; 9.4%), limonene (6.8; 18.7%), trans-ocimene (6.7; 6.1%), and β-myrcene (4.5; 4.4%). the antimicrobial activities ...201626948682
multiple brain abscesses due to aspergillus fumigatus in a patient with liver cirrhosis: a case report.invasive cerebral aspergillosis always developed in immunocompromised host. early diagnosis may save life in this critical condition; however, it is difficult to reach. herein, we presented an unusual case of invasive cerebral aspergillosis in a cirrhotic patient. a 47-year-old man presented with progressive deterioration of consciousness for three days. the patient had a history of alcoholic liver cirrhosis, child-pugh class c. magnetic resonance imaging (mri) of brain showed multi-focal parenc ...201626945363
[identification of microorganisms related to chronic rhinosinusitis in adult patients with variable common immunodeficiency].the prevalence of chronic rhinosinusitis in adult patients with common variable immunodeficiency (cvid) is 52%. the patients with cvid show higher incidence of chronic rhinosinusitis, which is an inflammatory disease that affects the lining of one or more paranasal sinuses and nasal cavity.201626943827
in silico analysis revealed high-risk single nucleotide polymorphisms in human pentraxin-3 gene and their impact on innate immune response against microbial pathogens.pentraxin-3 (ptx-3) protein is an evolutionary conserved protein that acts as a soluble pattern-recognition receptor for pathogens and plays important role in innate immune response. it recognizes various pathogens by interacting with extracellular moieties such as glactomannan of conidia (aspergillus fumigatus), lipopolysaccharide of pseudomonas aeruginosa, streptococcus pneumonia and salmonella typhimurium. thus, ptx-3 protein helps to clear these pathogens by activating downstream innate immu ...201626941719
identification of aspergillus fumigatus multidrug transporter genes and their potential involvement in antifungal resistance.aspergillus fumigatus can cause severe fatal invasive aspergillosis in immunocompromised patients but is also found in the environment. a. fumigatus infections can be treated with antifungals agents among which azole and echinocandins. resistance to the class of azoles has been reported not only from patient samples but also from environmental samples. azole resistance mechanisms involve for most isolates alterations at the site of the azole target (cyp51a); however, a substantial number of isol ...201626933209
galactosaminogalactan of aspergillus fumigatus, a bioactive fungal polymer.galactosaminogalactan (gag) is an extracellular polysaccharide produced by the mycelium of the opportunistic human fungal pathogen aspergillus fumigatus gag is the first polysaccharide described as a virulence factor in medical mycology. this review presents our current knowledge of the structural organization and biosynthesis of this polymer. the function of this molecule as an adhesin that also masks aspergillus pamps and the impact of gag on the modulation of the host immune response by induc ...201626932183
diversity and origins of indian multi-triazole resistant strains of aspergillus fumigatus.aspergillus fumigatus is a widespread opportunistic fungal pathogen causing an alarmingly high mortality rate in immunocompromised patients. nosocomial infections by drug-resistant a. fumigatus strains are of particular concern, and there is a pressing need to understand the origin, dispersal and long-term evolution of drug resistance in this organism. the objective of this study was to investigate the diversity and putative origins of triazole resistance of a. fumigatus from india. eighty-nine ...201626931802
biofilm filtrates of pseudomonas aeruginosa strains isolated from cystic fibrosis patients inhibit preformed aspergillus fumigatus biofilms via apoptosis.pseudomonas aeruginosa (pa) and aspergillus fumigatus (af) colonize cystic fibrosis (cf) patient airways. pa culture filtrates inhibit af biofilms, and pa non-cf, mucoid (muc-cf) and nonmucoid cf (nmuc-cf) isolates form an ascending inhibitory hierarchy. we hypothesized this activity is mediated through apoptosis induction. one af and three pa (non-cf, muc-cf, nmuc-cf) reference isolates were studied. af biofilm was formed in 96 well plates for 16 h ± pa biofilm filtrates. after 24 h, apoptosis ...201626930399
identification of ferrichrome- and ferrioxamine b-mediated iron uptake by aspergillus fumigatus.aspergillus fumigatus is an opportunistic fungal pathogen for immunocompromised patients, and genes involved in siderophore metabolism have been identified as virulence factors. recently, we identified the membrane transporters sit1 and sit2, which are putative virulence factors of a. fumigatus; sit1 and sit2 are homologous to yeast sit1, and sit1 and sit2 gene expression was up-regulated after iron depletion. when expressed heterologously in saccharomyces cerevisiae, sit1 and sit2 were localize ...201626929401
the role of basophil activation test in allergic bronchopulmonary aspergillosis and aspergillus fumigatus sensitization in cystic fibrosis patients.allergic bronchopulmonary aspergillosis (abpa) and aspergillus fumigatus sensitization (afs) are quite often observed in cystic fibrosis (cf) patients. the aim of this study was to evaluate the use of basophil activation test (bat) in these manifestations of hypersensitivity reactions.201626922860
inhibition of ceramide de novo synthesis by myriocin produces the double effect of reducing pathological inflammation and exerting antifungal activity against a. fumigatus airways infection.fungal infections develop in pulmonary chronic inflammatory diseases such as asthma, chronic obstructive pulmonary disease (copd) and cystic fibrosis (cf). the available antifungal drugs may fail to eradicate fungal pathogens, that can invade the lungs and vessels and spread by systemic circulation taking advantage of defective lung immunity. an increased rate of sphingolipid de novo synthesis, leading to ceramide accumulation, was demonstrated in cf and copd inflamed lungs. the inhibitor of sph ...201626922830
synthesis of newer 1,2,3-triazole linked chalcone and flavone hybrid compounds and evaluation of their antimicrobial and cytotoxic activities.the present study was carried out in an attempt to synthesize a new class of antimicrobial and antiplasmodial agents by copper catalyzed click chemistry to afford 25 compounds 10-14(a-e) of 1,4-disubstituted-1,2,3-triazole derivatives of chalcones and flavones. the structures of the newly synthesized compounds were established by elemental analysis, ir, (1)h nmr, (13)c nmr and mass spectral data. the newly synthesized compounds were evaluated for their antibacterial activity against gram positiv ...201626922227
the contribution of aspergillus fumigatus stress responses to virulence and antifungal resistance.invasive aspergillosis has emerged as one of the most common life-threatening fungal disease of humans. the emergence of antifungal resistant pathogens represents a current and increasing threat to society. in turn, new strategies to combat fungal infection are urgently required. fungal adaptations to stresses experienced within the human host are a prerequisite for the survival and virulence strategies of the pathogen. here, we review the latest information on the signalling pathways in aspergi ...201626920884
recent advances in the understanding of the aspergillus fumigatus cell wall.over the past several decades, research on the synthesis and organization of the cell wall polysaccharides of aspergillus fumigatus has expanded our knowledge of this important fungal structure. besides protecting the fungus from environmental stresses and maintaining structural integrity of the organism, the cell wall is also the primary site for interaction with host tissues during infection. cell wall polysaccharides are important ligands for the recognition of fungi by the innate immune syst ...201626920883
developmental regulators in aspergillus fumigatus.the filamentous fungus aspergillus fumigatus is the most prevalent airborne fungal pathogen causing severe and usually fatal invasive aspergillosis in immunocompromised patients. this fungus produces a large number of small hydrophobic asexual spores called conidia as the primary means of reproduction, cell survival, propagation, and infectivity. the initiation, progression, and completion of asexual development (conidiation) is controlled by various regulators that govern expression of thousand ...201626920882
human fungal pathogens: why should we learn?human fungal pathogens that cause invasive infections are hidden killers, taking lives of one and a half million people every year. however, research progress in this field has not been rapid enough to effectively prevent or treat life-threatening fungal diseases. to update recent research progress and promote more active research in the field of human fungal pathogens, eleven review articles concerning the virulence mechanisms and host interactions of four major human fungal pathogens-candida a ...201626920875
adsorption characteristics and preparative separation of chaetominine from aspergillus fumigatus mycelia by macroporous resin.chaetominine (cha) is a quinazolinone alkaloid with strong anti-cancer activity produced by aspergillus fumigatus cy018. for recovering cha from a. fumigates efficiently, adsorption and desorption capacities of eight macroporous resins were tested in this work. based on batch experiments, xad-16 resin was revealed the best adsorption and desorption performance among all the tested resins. then, adsorption kinetics and adsorption isotherms were constructed on xad-16 resin, and the experimental da ...201626919448
aspergillus fumigatus and mesophilic moulds in air in the surrounding environment downwind of non-hazardous waste landfill sites.non-hazardous waste landfilling has the potential to release biological agents into the air, notably mould spores. some species, such as aspergillus fumigatus, may be a cause of concern for at-risk nearby residents. however, air concentration in the surrounding environment of non-hazardous waste landfill sites is poorly documented. an extensive sampling programme was designed to investigate the relationship between culturable mesophilic moulds and a. fumigatus concentrations in air and distance ...201626915642
synthesis, molecular docking and evaluation of antifungal activity of ni(ii), co(ii) and cu(ii) complexes of porphyrin core macromolecular ligand.porphyrin core dendrimeric ligand (l) was synthesized by rothemund synthetic route in which p-hydroxy benzaldehyde and pyrrole were fused together. the prepared ligand was complexed with ni(ii), cu(ii) and co(ii) ions, separately. both the ligand and its complexes were characterized by elemental analysis and spectroscopic studies (ft-ir, uv-vis, (1)hnmr). square planar geometries were proposed for cu(ii), ni(ii) and co(ii) ions in cobalt, nickel and copper complexes, respectively on the basis of ...201626911647
role of granulocyte-macrophage colony-stimulating factor signaling in regulating neutrophil antifungal activity and the oxidative burst during respiratory fungal challenge.granulocyte-macrophage colony-stimulating factor (gm-csf) is a pleiotropic cytokine that plays a critical role in regulating myeloid cell host defense. in this study, we demonstrated that gm-csf signaling plays an essential role in antifungal defense against aspergillus fumigatus. mice that lack the gm-csf receptor β chain (gm-csfrβ) developed invasive hyphal growth and exhibited impaired survival after pulmonary challenge with a. fumigatus conidia. gm-csfrβ signaling regulated the recruitment o ...201626908736
the aspergillus fumigatus damage resistance protein family coordinately regulates ergosterol biosynthesis and azole susceptibility.ergosterol is a major and specific component of the fungal plasma membrane, and thus, the cytochrome p450 enzymes (erg proteins) that catalyze ergosterol synthesis have been selected as valuable targets of azole antifungals. however, the opportunistic pathogen aspergillus fumigatus has developed worldwide resistance to azoles largely through mutations in the cytochrome p450 enzyme cyp51 (erg11). in this study, we demonstrate that a cytochrome b5-like heme-binding damage resistance protein (dap) ...201626908577
molecular characterization of gβ-like protein cpcb involved in antifungal drug susceptibility and virulence in a. fumigatus.aspergillus fumigatus is an airborne human fungal pathogen that can survive in a wide range of environmental condition. g protein complex transduces external signals from a variety of stimuli outside a cell to its interior effectors in all eukaryotes. gβ-like cpcb (cross pathway control b) belongs to a wd40 repeat protein family with the conserved g-h and w-d residues. previous studies have demonstrated that gβ-like proteins cooperate with related signal transduction proteins to function during ...201626903985
assessment of the cytotoxic and apoptotic eἀects of chaetominine in a human leukemia cell line.chaetominine is a quinazoline alkaloid originating from the endophytic fungus aspergillus fumigatus cy018. in this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia k562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. chaetominine inhibited k562 cell growth, with an ic50 value of 35 nm, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. the high apoptosis rates, mo ...201626902083
aspergillus pcr in serum for the diagnosis, follow-up and prognosis of invasive aspergillosis in neutropenic and nonneutropenic patients.we evaluated the usefulness of a serum aspergillus pcr assay for the diagnosis and prognosis of invasive aspergillosis in a study involving 941 patients for a total of 5146 serum samples. fifty-one patients had proven/probable aspergillosis. we compared galactomannan (gm), pcr and mycologic analysis of pulmonary samples in both neutropenic and nonneutropenic patients. pcr performed in serum yielded 66.7% sensitivity, 98.7% specificity, 75.6% positive predictive value and 98.0% negative predictiv ...201626899830
multi-azole resistant aspergillus fumigatus harboring cyp51a tr46/y121f/t289a isolated in japan.multi-azole resistant aspergillus fumigatus carrying tr46/y121f/t289a was isolated from a patient in japan in dec 2013. this strain grouped into the same clade of the ones which were clinically isolated in france and germany. a. fumigatus harboring this mutation could be rapidly diffused outside the eurasian continent.201626898666
three-dimensional structures of two heavily n-glycosylated aspergillus sp. family gh3 β-d-glucosidases.the industrial conversion of cellulosic plant biomass into useful products such as biofuels is a major societal goal. these technologies harness diverse plant degrading enzymes, classical exo- and endo-acting cellulases and, increasingly, cellulose-active lytic polysaccharide monooxygenases, to deconstruct the recalcitrant β-d-linked polysaccharide. a major drawback with this process is that the exo-acting cellobiohydrolases suffer from severe inhibition from their cellobiose product. β-d-glucos ...201626894673
subchronic exposures to fungal bioaerosols promotes allergic pulmonary inflammation in naïve mice.epidemiological surveys indicate that occupants of mold contaminated environments are at increased risk of respiratory symptoms. the immunological mechanisms associated with these responses require further characterization.201626892490
raca-mediated ros signaling is required for polarized cell differentiation in conidiogenesis of aspergillus fumigatus.conidiophore development of fungi belonging to the genus aspergillus involves dynamic changes in cellular polarity and morphogenesis. synchronized differentiation of phialides from the subtending conidiophore vesicle is a good example of the transition from isotropic to multi-directional polarized growth. here we report a small gtpase, raca, which is essential for reactive oxygen species (ros) production in the vesicle as well as differentiation of phialides in aspergillus fumigatus. we found th ...201626890813
azide-enolate 1,3-dipolar cycloaddition in the synthesis of novel triazole-based miconazole analogues as promising antifungal agents.seven miconazole analogs involving 1,4,5-tri and 1,5-disubstituted triazole moieties were synthesized by azide-enolate 1,3-dipolar cycloaddition. the antifungal activity of these compounds was evaluated in vitro against four filamentous fungi, including aspergillus fumigatus, trichosporon cutaneum, rhizopus oryzae, and mucor hiemalis as well as three species of candida spp. as yeast specimens. these pre-clinical studies suggest that compounds 4b, 4d and 7b can be considered as drug candidates fo ...201626890112
prospective evaluation of a new aspergillus igg enzyme immunoassay kit for diagnosis of chronic and allergic pulmonary aspergillosis.anti-aspergillus igg antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (cpa) and allergic bronchopulmonary aspergillosis (abpa). we compared the performance of a new commercial enzyme immunoassay (eia) (bordier affinity products) with that of the bio-rad and virion\serion eias. this assay is novel in its association of two recombinant antigens with somatic and metabolic antigens of aspergillus fumigatus in a prospective multicenter study, 436 serum samples ...201626888904
towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity.gliotoxin (gt) is a mycotoxin produced by some species of ascomycete fungi including the opportunistic human pathogen aspergillus fumigatus. in order to produce gt the host organism needs to have evolved a self-protection mechanism. gt contains a redox-cycling disulfide bridge that is important in mediating toxicity. recently is has been demonstrated that a. fumigatus possesses a novel thiomethyltransferase protein called gtma that has the ability to thiomethylate gt in vivo, which aids the orga ...201628357342
azole resistance of aspergillus fumigatus in immunocompromised patients with invasive aspergillosis. 201626691166
azole resistance of aspergillus fumigatus in immunocompromised patients with invasive aspergillosis. 201626690934
multiple fungicide-driven alterations in azole-resistant aspergillus fumigatus, colombia, 2015. 201626690795
horizontal acquisition of toxic alkaloid synthesis in a clade of plant associated fungi.clavicipitaceae is a fungal group that comprises species that closely interact with plants as pathogens, parasites or symbionts. a key factor in these interactions is the ability of these fungi to synthesize toxic alkaloid compounds that contribute to the protection of the plant host against herbivores. some of these compounds such as ergot alkaloids are toxic to humans and have caused important epidemics throughout history. the gene clusters encoding the proteins responsible for the synthesis o ...201626688468
comparison of six aspergillus-specific igg assays for the diagnosis of chronic pulmonary aspergillosis (cpa).chronic pulmonary aspergillosis (cpa) is estimated to affect 3 million persons worldwide. aspergillus-specific igg is a key component in cpa diagnosis. we aimed to establish the optimal diagnostic cut offs for cpa and the comparative performance of six assays in this context.201626680697
detection of airway colonization by aspergillus fumigatus by use of electronic nose technology in patients with cystic fibrosis.currently, there is no noninvasive test that can reliably diagnose early invasive pulmonary aspergillosis (ia). an electronic nose (enose) can discriminate various lung diseases through an analysis of exhaled volatile organic compounds. we recently published a proof-of-principle study showing that patients with prolonged chemotherapy-induced neutropenia and ia have a distinct exhaled breath profile (or breathprint) that can be discriminated with an enose. an enose is cheap and noninvasive, and i ...201626677251
highly efficient and easy protease-mediated protein purification.as both research on and application of proteins are rarely focused on the resistance towards nonspecific proteases, this property remained widely unnoticed, in particular in terms of protein purification and related fields. in the present study, diverse aspects of protease-mediated protein purification (pmpp) were explored on the basis of the complementary proteases trypsin and proteinase k as well as the model proteins green fluorescent protein (gfp) from aequorea victoria, lipase a from candid ...201626671615
human neutrophils use different mechanisms to kill aspergillus fumigatus conidia and hyphae: evidence from phagocyte defects.neutrophils are known to play a pivotal role in the host defense against aspergillus infections. this is illustrated by the prevalence of aspergillus infections in patients with neutropenia or phagocyte functional defects, such as chronic granulomatous disease. however, the mechanisms by which human neutrophils recognize and kill aspergillus are poorly understood. in this work, we have studied in detail which neutrophil functions, including neutrophil extracellular trap (net) formation, are invo ...201626718340
purification and characterization of polygalacturonase from aspergillus fumigatus mtcc 2584 and elucidating its application in retting of crotalaria juncea fiber.polygalacturonases represents an important member of pectinases group of enzymes with diverse industrial applications and is widely distributed among fungi, bacteria, yeasts, plants and some plant parasitic nematodes. an endo-polygalacturonase from a new fungal source aspergillus fumigatus mtcc 2584 was produced under solid-state fermentation conditions and was purified simply by acetone precipitation and gel-filtration chromatography technique. the approximate molecular weight of the purified p ...201628330273
enzymatic production of glucosamine and chitooligosaccharides using newly isolated exo-β-d-glucosaminidase having transglycosylation activity.exochitosanase secreting fungus (a. fumigatus iit-004) was isolated from fish waste using 1 % (w/v) chitosan as sole carbon source after multistage screening. chitosan-dependent exochitosanase enzyme production (6 iu ml(-1)) in log phase of growth (chitosan utilization rate 0.11 g g(-1) cell h(-1)) was observed for aspergillus fumigatus in chitosan minimal salt medium and there was no enzyme production in glucose medium. enzyme production was found to be extracellular and subjected to purificati ...201628330083
in vitro resistance of aspergillus fumigatus to azole farm fungicide.azole resistance in aspergillus fumigatus is mainly due to a point mutation in the 14α-sterol demethylase (cyp51a) gene, which encodes the target of azole fungicides. moreover, overexpression of cyp51b or multidrug resistance (mdr) gene is supposedly related to the mechanism of azole resistance in a. fumigatus. in this study, we tried to induce resistance to tetraconazole, an azole fungicide, in strains of a. fumigatus from a farm and then investigated mutation and expression of their cyp51a, cy ...201626711232
tolerance to silver of an aspergillus fumigatus strain able to grow on cyanide containing wastes.we studied the strategy of an aspergillus fumigatus strain able to grow on metal cyanide wastes to cope with silver. the tolerance test revealed that the minimum inhibitory concentration of ag(i) was 6mm. in 1mm agno3 aqueous solution the fungus was able to reduce and sequestrate silver into the cell in the form of nanoparticles as evidenced by the change in color of the biomass and electron microscopy observations. extracellular silver nanoparticle production also occurred in the filtrate solut ...201626705888
late aspergilloma of a renal allograft without need for operative management: a case report and review of the literature.aspergillus infection localized to the renal allograft is a rare and potentially life-threatening infection and typically requires a combination of operative and medical management. we report the case of a renal allograft aspergilloma in a renal transplant patient presenting 2 years post transplant, successfully managed non-surgically. to our knowledge, this is the first report of a patient presenting with an allograft aspergilloma so long after transplantation and being successfully managed wit ...201626751414
aspergillus cell wall melanin blocks lc3-associated phagocytosis to promote pathogenicity.concealing pathogen-associated molecular patterns (pamps) is a principal strategy used by fungi to avoid immune recognition. surface exposure of pamps during germination can leave the pathogen vulnerable. accordingly, β-glucan surface exposure during aspergillus fumigatus germination activates an atg5-dependent autophagy pathway termed lc3-associated phagocytosis (lap), which promotes fungal killing. we found that lap activation also requires the genetic, biochemical or biological (germination) ...201626749442
aspergillus otitis in small animals--a retrospective study of 17 cases.aspergillus spp. are saprophytic opportunistic fungal organisms and are a common cause of otomycosis in humans. although there have been case reports of aspergillus otitis externa in dogs, to the best of the authors' knowledge, this is the first retrospective case series describing aspergillus otitis in dogs and cats.201626748885
identification and characterization of haemofungin, a novel antifungal compound that inhibits the final step of haem biosynthesis.during recent decades, the number of invasive fungal infections among immunosuppressed patients has increased significantly, whereas the number of effective systemic antifungal drugs remains low and unsatisfactory. the aim of this study was to characterize a novel antifungal compound, cw-8/haemofungin, which we previously identified in a screen for compounds affecting fungal cell wall integrity.201626747101
serological diagnosis of allergic bronchopulmonary mycosis: progress and challenges.prompt diagnosis of allergic bronchopulmonary mycosis (abpm) is an important clinical issue in preventing irreversible lung damage. therefore, a good serological marker for the diagnosis of abpm is desired in clinical practice. the measurement of ige antibody to crude aspergillus fumigatus allergen is considered the first step in screening asthmatic patients for allergic bronchopulmonary aspergillosis (abpa). however, presence of ige to a. fumigatus does not always indicate genuine sensitization ...201626740298
the iron-responsive microsomal proteome of aspergillus fumigatus.aspergillus fumigatus is an opportunistic fungal pathogen. siderophore biosynthesis and iron acquisition are essential for virulence. yet, limited data exist with respect to the adaptive nature of the fungal microsomal proteome under iron-limiting growth conditions, as encountered during host infection. here, we demonstrate that under siderophore biosynthetic conditions--significantly elevated fusarinine c (fsc) and triacetylfusarinine c (tafc) production (p<0.0001), extensive microsomal proteom ...201626739764
draft genome sequence of the pathogenic filamentous fungus aspergillus lentulus ifm 54703t.aspergillus lentulus, a sibling species of aspergillus fumigatus, has been reported as a causative agent of aspergillosis, and exhibited low susceptibility to azole. here, we present the draft genome sequence of a. lentulus strain ifm 54703(t) for the first time.201626769945
aspergillus fumigatus produces two arabinofuranosidases from glycosyl hydrolase family 62: comparative properties of the recombinant enzymes.the genes of two α-l-arabinofuranosidases (abfi and ii) from family gh 62 have been identified in the genome of aspergillus fumigatus wmo. both genes have been expressed in pichia pastoris and the enzymes have been purified and characterized. abfi is composed of 999 bp, does not contain introns and codes for a protein (abfi) of 332 amino acid residues. abfii has 1246 bp, including an intron of 51 bp; the protein abfii has 396 amino acid residues; it includes a family 1 carbohydrate-binding modul ...201626769705
immunomodulatory effect of mesenchymal stem cells on the immune response of macrophages stimulated by aspergillus fumigatus conidia.mesenchymal stem cells (mscs) are known to exert potent immunosuppression and anti-inflammatory effects. there is growing interest in their use for immunotherapy for controlling inflammation as well as acute organ injury. however, there are few reports regarding msc's immunomodulatory effects in the settings of fungal infection. in this study, we attempted to examine the immunomodulatory effects of mscs in response to aspergillus fumigatus we measured the cytokine response of murine mscs on the ...201626768375
cyp51a-based mechanism of azole resistance in aspergillus fumigatus: illustration by a new 3d structural model of aspergillus fumigatus cyp51a protein.mutations of cyp51a protein (cytochrome p450 14-α sterol demethylase) play a central role in the azole resistance of aspergillus fumigatus the available structural models of cyp51a protein ofa. fumigatus are built based on that of homo sapiens and that of mycobacterium tuberculosis, of which the amino acid homology is only 38% and 29% compared with cyp51a protein ofa. fumigatus, respectively. in the present study, we constructed a new 3d structural model ofa. fumigatus cyp51a protein based on a ...201626768370
aspergillus fumigatus promotes t helper type 2 responses through thymic stromal lymphopoietin production by human corneal epithelial cells.fungal keratitis is a major cause of blindness. to understand the mechanism of both innate and adaptive immunity in corneal infection is of great significance in the treatment and prevention of fungal keratitis. our previous study concerned innate immunity. here, we explored the potential role of thymic stromal lymphopoietin (tslp) in adaptive immunity of fungal keratitis.201626759304
microbial colonization and lung function in adolescents with cystic fibrosis.with intensified antibiotic therapy and longer survival, patients with cystic fibrosis (cf) are colonized with a more complex pattern of bacteria and fungi. however, the clinical relevance of these emerging pathogens for lung function remains poorly defined. the aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with cf. microbial colonization patterns and lung function parameters were assessed in 770 adolescent ...201626856310
epidemiology and molecular mechanisms of antifungal resistance in candida and aspergillus.the significant increase in the use of antifungal agents, both for the treatment of candidiasis and invasive aspergillosis and as azole fungicides in agricultural crop protection has resulted in the emergence of resistant clinical isolates, particularly to triazoles and echinocandins. notably, among isolates that were primarily sensitive to fluconazole such as candida parapsilosis and candida tropicalis have witnessed an emerging resistance development. also for echinocandins, the occurrence of ...201626810669
effect of media modified to mimic cystic fibrosis sputum on the susceptibility of aspergillus fumigatus, and the frequency of resistance at one center.studies of cystic fibrosis (cf) patient exacerbations attributed topseudomonas aeruginosainfection have indicated a lack of correlation of outcome within vitrosusceptibility results. one explanation is that the media used for testing do not mimic the airway milieu, resulting in incorrect conclusions. therefore, media have been devised to mimic cf sputum.aspergillus fumigatusis the leading fungal pathogen in cf, and susceptibility testing is also used to decide therapeutic choices. we assessed wh ...201626810647
sequential inactivation of gliotoxin by the s-methyltransferase tmta.the epipolythiodioxopiperazine (etp) gliotoxin mediates toxicity via its reactive thiol groups and thereby contributes to virulence of the human pathogenic fungus aspergillus fumigatus. self-intoxication of the mold is prevented either by reversible oxidation of reduced gliotoxin or by irreversible conversion to bis(methylthio)gliotoxin. the latter is produced by the s-methyltransferase tmta and attenuates etp biosynthesis. here, we report the crystal structure of tmta in complex with s-(5'-aden ...201626808594
immunopet/mr imaging allows specific detection of aspergillus fumigatus lung infection in vivo.invasive pulmonary aspergillosis (ipa) is a life-threatening lung disease caused by the fungus aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. we developed and tested a novel probe for noninvasive detection of a. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunopet/mr) imaging. administration of a [(64)cu]d ...201626787852
exploration of sulfur assimilation of aspergillus fumigatus reveals biosynthesis of sulfur-containing amino acids as a virulence determinant.fungal infections are of major relevance due to the increased numbers of immunocompromised patients, frequently delayed diagnosis, and limited therapeutics. to date, the growth and nutritional requirements of fungi during infection, which are relevant for invasion of the host, are poorly understood. this is particularly true for invasive pulmonary aspergillosis, as so far, sources of (macro)elements that are exploited during infection have been identified to only a limited extent. here, we have ...201626787716
occurrence of mycotoxins and yeasts and moulds identification in corn silages in tropical climate.this study was aimed to identify yeasts and moulds as well as to detect mycotoxin in corn silages in southern minas gerais, brazil.201626787003
cd203c in patients with cystic fibrosis and allergy to aspergillus fumigatus. 201626782973
chronic aspergillus fumigatus colonization of the pediatric cystic fibrosis airway is common and may be associated with a more rapid decline in lung function.filamentous fungi are commonly isolated from the respiratory tract of cf patients, but their clinical significance is uncertain and the reported incidence variable. we report on the degree of aspergillus fumigatus airway colonization in a tertiary pediatric cf cohort, evaluate the sensitivity of routine clinical sampling at detecting a. fumigatus, and compare lung function of a. fumigatus-colonized and non-colonized children.we carried out an 8-year retrospective cohort analysis using local data ...201626782645
de-repression of csp-1 activates adaptive responses to antifungal azoles.antifungal azoles are the major drugs that are used to treat fungal infections. this study found that in response to antifungal azole stress, neurospora crassa could activate the transcriptional responses of many genes and increase azole resistance by reducing the level of conidial separation 1 (csp-1), a global transcription repressor, at azole-responsive genes. the expression of csp-1 was directly activated by the transcription factors wc-1 and wc-2. upon ketoconazole (ktc) stress, the transcr ...201626781458
quaternary ammonium biocides as antimicrobial agents protecting historical wood and brick.quaternary ammonium compounds (qacs) are widely used in disinfection of water, surfaces and instruments as well as in textile, leather and food industries because of their relatively low toxicity, broad antimicrobial spectrum, non-volatility and chemical stability. due to these advantages, qacs are also used in restoration and can be applied on historical material. the aim of this study was to determine the usefulness of biocides based on quaternary ammonium salts and containing various excipien ...201626629794
regulation of mitochondrial inner membrane fusion: divergent evolution with similar solutions?continuous mitochondrial fusion and fission define the dynamic shape of mitochondria. one essential player of mitochondrial fusion is the conserved inner membrane dynamin-like gtpase mgm1/opa1. limited proteolysis of this protein has been proposed as a mechanism to separate and subsequently eliminate dysfunctional parts from the mitochondrial network. here, i briefly summarize our current knowledge about the underlying proteolytic processing steps in mammals, baker's yeast, schizosaccharomyces p ...201626613727
trpe feedback mutants reveal roadblocks and conduits toward increasing secondary metabolism in aspergillus fumigatus.small peptides formed from non-ribosomal peptide synthetases (nrps) are bioactive molecules produced by many fungi including the genus aspergillus. a subset of nrps utilizes tryptophan and its precursor, the non-proteinogenic amino acid anthranilate, in synthesis of various metabolites such as aspergillus fumigatus fumiquinazolines (fqs) produced by the fmq gene cluster. the a. fumigatus genome contains two putative anthranilate synthases - a key enzyme in conversion of anthranilic acid to trypt ...201626701311
highly efficient crispr mutagenesis by microhomology-mediated end joining in aspergillus fumigatus.filamentous fungi have a dominant nonhomologous-end joining (nhej) dna repair pathway, which results in the majority of transformed progenies having random heterologous insertion mutagenesis. thus, lack of a versatile genome-editing tool prevents us from carrying out precise genome editing to explore the mechanism of pathogenesis. moreover, clinical isolates that have a wild-type ku80 background without any selection nutrition marker especially suffer from low homologous integration efficiency. ...201626701308
the spectrum of allergic fungal diseases of the upper and lower airways.fungi cause a wide spectrum of fungal diseases of the upper and lower airways. there are three main phyla involved in allergic fungal disease: (1) ascomycota (2) basidiomycota (3) zygomycota. allergic fungal rhinosinusitis (afrs) causes chronic rhinosinusitis symptoms and is caused predominantly by aspergillus fumigatus in india and bipolaris in the united states. the recommended treatment approach for afrs is surgical intervention and systemic steroids. allergic bronchopulmonary aspergillosis ( ...201626776889
ptx3, a humoral pattern recognition molecule at the interface between microbe and matrix recognition.innate immunity consists of a cellular and a humoral arm. ptx3 is a fluid patter recognition molecule (prm) with antibody-like properties. gene targeted mice and genetic associations in humans suggest that ptx3 plays a non-redundant role in resistance against selected pathogens (e.g. aspergillus fumigatus, pseudomonas aeruginosa, uropathogenic escherichia coli) and in the regulation of inflammation. ptx3 acts as an extrinsic oncosuppressor by taming complement elicited tumor-promoting inflammati ...201626650391
diagnosis and management of aspergillosis in the netherlands: a national survey.a survey of diagnosis and treatment of invasive aspergillosis was conducted in eight university medical centers (umcs) and eight non-academic teaching hospitals in the netherlands. against a background of emerging azole resistance in aspergillus fumigatus routine resistance screening of clinical isolates was performed primarily in the umcs. azole resistance rates at the hospital level varied between 5% and 10%, although rates up to 30% were reported in high-risk wards. voriconazole remained firs ...201626648179
hydrogen peroxide-induced secondary necrosis in conidia of aspergillus fumigatus.aspergillus fumigatus conidia have been linked to severe aspergillosis in immunocompromised patients. recently, the cytotoxic effect of secondary metabolites from a. fumigatus conidia was reported. in the present work, a methodology used to detect cell death markers in fungal hyphae was adapted to study conidia cell death. additionally, the mechanism of h2o2-induced cell death was studied in a. fumigatus conidia for the first time. data presented in this work reveal that the h2o2-induced conidia ...201626639790
mycologic endocrinology.the interactions of fungi and chemical messenger molecules, hormones or pheromones, are addressed in this chapter. these interactions include mammalian fungal pathogens, also plant pathogens, or non-pathogenic fungi, which can result in functional responses in receptor- or non-receptor-mediated fashions. endogenous ligands in the fungi have been demonstrated to be important for mating in a number of systems. mammalian hormones have been demonstrated to have stimulatory or inhibitory effects on g ...201626589227
blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis.the diagnosis of cystic fibrosis (cf) patients with allergic bronchopulmonary aspergillosis (abpa) is clinically challenging, due to the absence of an objective biological test. since blood basophils play a major role in allergic responses, we hypothesised that changes in their surface activation pattern discriminate between cf patients with and without abpa.we conducted a prospective longitudinal study (stanford cohort) comparing basophil activation test cd203c levels by flow cytometry before a ...201626585435
zinc and manganese chelation by neutrophil s100a8/a9 (calprotectin) limits extracellular aspergillus fumigatus hyphal growth and corneal infection.calprotectin, a heterodimer of s100a8 and s100a9, is an abundant neutrophil protein that possesses antimicrobial activity primarily because of its ability to chelate zinc and manganese. in the current study, we showed that neutrophils from calprotectin-deficient s100a9(-/-) mice have an impaired ability to inhibit aspergillus fumigatus hyphal growth in vitro and in infected corneas in a murine model of fungal keratitis; however, the ability to inhibit hyphal growth was restored in s100a9(-/-) mi ...201626582948
role of the mannose receptor during aspergillus fumigatus infection and interaction with dectin-1 in corneal epithelial cells.to investigate the expression and function of the mannose receptor (mr) and to explore its interaction with dectin-1 in human corneal epithelial cells (hcecs) exposed to aspergillus fumigatus.201626606296
mutant characterization and in vivo conditional repression identify aromatic amino acid biosynthesis to be essential for aspergillus fumigatus virulence.pathogenicity of the saprobe aspergillus fumigatus strictly depends on nutrient acquisition during infection, as fungal growth determines colonisation and invasion of a susceptible host. primary metabolism has to be considered as a valid target for antimycotic therapy, based on the fact that several fungal anabolic pathways are not conserved in higher eukaryotes. to test whether fungal proliferation during invasive aspergillosis relies on endogenous biosynthesis of aromatic amino acids, defined ...201626605426
in vivo veritas: aspergillus fumigatus proliferation and pathogenesis--conditionally speaking. 201626695225
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