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are we there yet? recent progress in the molecular diagnosis and novel antifungal targeting of aspergillus fumigatus and invasive aspergillosis. 201324204250
emergence of azole-resistant aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health. 201324204249
allergic bronchopulmonary aspergillosis in asthma: epidemiological, clinical and therapeutic issues.allergic bronchopulmonary aspergillosis (abpa) is a complex pulmonary disorder caused by immunologic reactions to antigens released by aspergillus fumigatus, a ubiquitous fungi colonizing the tracheobronchial tree of asthmatic patients. the clinical presentation is usually poorly controlled asthma, recurrent pulmonary opacities and bronchiectasis. the prevalence of abpa in asthma clinics may be as high as 13% with a global burden of almost 5 million patients. a. fumigatus-specific ige level is t ...201324199804
angiogenesis at the mold-host interface: a potential key to understanding and treating invasive aspergillosis.invasive aspergillosis (ia) in neutropenic patients is characterized by angioinvasion, intravascular thrombosis and tissue infarction, features that lead to sequestration of infected tissue and impaired fungal clearance. recent research has shown that host angiogenesis, the homeostatic compensatory response to tissue hypoxia, is downregulated by aspergillus fumigatus secondary metabolites. a. fumigatus metabolites inhibit multiple key angiogenic mediators, notably basic fgf, vegf and their respe ...201324199803
expression and activity of catalases is differentially affected by gpaa (ga) and flba (regulator of g protein signaling) in aspergillus fumigatus.vegetative growth signaling of the opportunistic human pathogenic fungus aspergillus fumigatus is mediated by gpaa (gα). flba is a regulator of g protein signaling, which attenuates gpaa-mediated growth signaling in this fungus. the flba deletion (δflba) and the constitutively active gpaa (gpaa(q204l)) mutants exhibit enhanced proliferation, precocious autolysis, and reduced asexual sporulation. in this study, we demonstrate that both mutants also show enhanced tolerance against h2o2 and their r ...201324198669
the roda hydrophobin on aspergillus fumigatus spores masks dectin-1- and dectin-2-dependent responses and enhances fungal survival in vivo.aspergillus and fusarium species are important causes of fungal infections worldwide. airborne spores (conidia) of these filamentous fungi express a surface protein that confers hydrophobicity (hydrophobin) and covers cell wall components that would otherwise induce a host immune cell response. using a mutant aspergillus fumigatus strain (δroda) that does not express the roda hydrophobin, and aspergillus and fusarium conidia from clinical isolates that were treated with hydrofluoric acid (which ...201323926321
the crucial role of iron uptake in aspergillus fumigatus virulence.aspergillus fumigatus is an opportunistic fungal pathogen that causes life-threatening infections in immunocompromised individuals. siderophore-mediated iron acquisition has been shown to be essential for virulence. new studies have revealed that enzymes involved in siderophore biosynthesis and uptake are compartmentalized in peroxisomes and endosome-like vesicles, respectively. gene and protein expression studies have revealed coordinated regulation of siderophore and sterol metabolism linked t ...201323962820
effect of hay dust extract and cyathostomin antigen stimulation on cytokine expression by pbmc in horses with recurrent airway obstruction.equine recurrent airway obstruction (rao) is an inflammatory, obstructive airway disease induced by exposure of susceptible horses to inhaled organic dust particles. the immunological process underlying rao is still unclear. previous studies have shown that rao is linked to the interleukin-4 receptor (il-4r) gene in one warmblood family (f1), but not in another (f2). it has also been shown that in f1, but not in f2, rao is associated with resistance against parasites, suggesting that this associ ...201323972861
allergic bronchopulmonary aspergillosis in garden waste (compost) collectors--occupational implications.the separation of rotting garden material from general domestic waste and its collection for processing in industrial composting sites is a relatively new industry in the uk. two cases of allergic bronchopulmonary aspergillosis and the results of health surveillance are described in a team of 28 garden waste (compost) collectors. a few cases of extrinsic allergic alveolitis due to aspergillus fumigatus have previously been reported in compost workers. in the absence of any guidance from research ...201323975883
identification and quantification of fungi and mycotoxins from pu-erh tea.pu-erh tea originates from the province of yunnan in south-western china. as this tea is produced by so called aspergillus post-fermentation the question arises which molds and mycotoxins may be found in this tea. in total 36 samples of pu-erh tea were investigated for their content of filamentous fungi and the mycotoxins aflatoxins b1, b2, g1, and g2, fumonisins b1, b2, and b3, and ochratoxin a. fungi were isolated from all samples in a concentration of 1.0×10(1) to 2.6×10(6) colony forming uni ...201323973844
impact of in vivo triazole and echinocandin combination therapy for invasive pulmonary aspergillosis: enhanced efficacy against cyp51 mutant isolates.previous studies examining combination therapy for invasive pulmonary aspergillosis (ipa) have revealed conflicting results, including antagonism, indifference, and enhanced effects. the most commonly employed combination for this infection includes a mold-active triazole and echinocandin. few studies have evaluated combination therapy from a pharmacodynamic (pd) perspective, and even fewer have examined combination therapy against both wild-type and azole-resistant cyp51 mutant isolates. the cu ...201323959322
outcome of tini stent treatments in symptomatic central airway stenoses caused by aspergillus fumigatus infections after lung transplantation.central airway stenoses due to aspergillus fumigatus infections have been a significant cause of morbidity and mortality after lung transplantation. we reviewed our experience using self-expandable braided tini-metallic stents in the management of 4 single-lung transplant recipients with central airways stenoses between january 2003 and june 2010.201323953550
anterior and pan-endophthalmitis caused by candida albicans and aspergillus fumigatus: report of two cases.we report two posttraumatic fungal endophthalmitis cases with anterior and entire segment involvement caused, respectively, by candida albicans and aspergillus fumigatus. the anterior endophthalmitis induced by c. albicans presented multifocal lesions with hyphael structures in anterior chamber, but without involvement of posterior vitreous. the pan-endophthalmitis caused by a. fumigatus displayed significant hypopyon and vitritis. treatment strategies are anterior chamber cleaning for anterior ...201323948966
an inhalation model of allergic fungal asthma: aspergillus fumigatus-induced inflammation and remodeling in allergic airway disease.the ability to accurately mimic normal processes for sensitization and allergen challenge in an experimental animal model are useful in that they allow researchers to critically manipulate the complex interactions of multiple cell types. in the context of the allergic lung, multiple cell types form complex cellular networks and function to regulate a variety of temporal and spatial changes. mouse models of allergic airway disease have proven to be highly useful for dissecting these complex inter ...201323943453
microcalorimetry assay for rapid detection of voriconazole resistance in aspergillus fumigatus.we describe a calorimetric assay for detection of voriconazole-resistant aspergillus fumigatus within 8 h. among 27 genetically distinct strains, all 21 resistant and all 6 susceptible strains were correctly identified by measurement of fungal heat production in the presence of voriconazole. this proof-of-concept study demonstrates the potential of microcalorimetry for rapid detection of azole resistance in a. fumigatus.201323939893
gβ-like cpcb plays a crucial role for growth and development of aspergillus nidulans and aspergillus fumigatus.growth, development, virulence and secondary metabolism in fungi are governed by heterotrimeric g proteins (g proteins). a gβ-like protein called gib2 has been shown to function as an atypical gβ in gpa1-camp signaling in cryptococcus neoformans. we found that the previously reported cpcb (cross pathway control b) protein is the ortholog of gib2 in aspergillus nidulans and aspergillus fumigatus. in this report, we further characterize the roles of cpcb in governing growth, development and toxige ...201323936193
t-2 toxin impairs antifungal activities of chicken macrophages against aspergillus fumigatus conidia but promotes the pro-inflammatory responses.aspergillosis is the most common fungal disease of the avian respiratory tract and is caused primarily by aspergillus fumigatus. the respiratory macrophages provide important defence against aspergillosis. t-2 toxin (t-2), a trichothecene mycotoxin produced by fusarium spp. in improperly stored agricultural products, has immunomodulatory effects. we studied the impact of t-2 on the antifungal response of the chicken macrophage cell line hd-11 against a. fumigatus infection. the macrophages were ...201323930935
dectin-2 is predominately macrophage restricted and exhibits conspicuous expression during aspergillus fumigatus invasion in human lung.we investigated the features of dectin-2 expression both at transcriptional and translational levels during aspergillus fumigatus infection in human lung. simultaneously, the expression of cd206 was assayed as an activated marker of alveolar macrophages. the characteristic of dectin-2 expression were then confirmed in monocyte-derived macrophages (mdm) after a. fumigatus stimulation by flow cytometry. we found that the expression of dectin-2 was low in normal lung, while it revealed a markedly u ...201323928558
camkii is essential for the proasthmatic effects of oxidation.increased reactive oxygen species (ros) contribute to asthma, but little is known about the molecular mechanisms connecting increased ros with characteristic features of asthma. we show that enhanced oxidative activation of the ca(2+)/calmodulin-dependent protein kinase (ox-camkii) in bronchial epithelium positively correlates with asthma severity and that epithelial ox-camkii increases in response to inhaled allergens in patients. we used mouse models of allergic airway disease induced by ovalb ...201323884469
imaging mass spectrometry of a coral microbe interaction with fungi.fungal infections are increasing worldwide, including in the aquatic environment. microbiota that coexist with marine life can provide protection against fungal infections by secretion of metabolites with antifungal properties. our laboratory has developed mass spectrometric methodologies with the goal of improving our functional understanding of microbial metabolites and guiding the discovery process of anti-infective agents from natural sources. ga40, a bacillus amyloliquefaciens strain isolat ...201323881443
transcriptomic and morphological profiling of aspergillus fumigatus af293 in response to antifungal activity produced by lactobacillus plantarum 16.the morphological effects of an antifungal activity produced by lactobacillus plantarum 16, a malt-production steep water isolate, on two food-associated fungi were examined microscopically. spore germination was completely inhibited in aspergillus fumigatus and rhizopus stolonifer upon treatment with concentrated cell-free supernatant (ccfs) of strain 16. furthermore, addition of antifungal ccfs to germ tubes and hyphae halted further development compared to untreated controls. transcriptome an ...201323876797
[bk or not bk? a misleading presentation]. 201323876207
activity of antifungal combinations against aspergillus species evaluated by isothermal microcalorimetry.we evaluated the activity of antifungals alone or in combination against aspergillus fumigatus and aspergillus terreus by real-time measurement of fungal growth-related heat production. amphotericin b, voriconazole, caspofungin, and anidulafungin were tested alone or in combination. heat production was measured in sabouraud dextrose broth containing 10(5)aspergillus conidia/ml for 48 h at 37 °c. antifungal activity was evaluated by measuring the heat detection time relative to the growth control ...201323871413
unraveling the nanoscale surface properties of chitin synthase mutants of aspergillus fumigatus and their biological implications.understanding the surface properties of the human opportunistic pathogen aspergillus fumigatus conidia is essential given the important role they play during the fungal interactions with the human host. although chitin synthases with myosin motor-like domain (csm) play a major role in cell wall biosynthesis, the extent to which deletion of the csm genes alter the surface structural and biophysical-biological properties of conidia is not fully characterized. we used three complementary atomic for ...201323870253
woronin bodies, their impact on stress resistance and virulence of the pathogenic mould aspergillus fumigatus and their anchoring at the septal pore of filamentous ascomycota.hyphae of filamentous ascomycota consist of compartments that are connected via septal pores. to avoid a dramatic loss of cellular content after wounding, fungi developed mechanisms to occlude their septal pores. in most pezizomycotina, so-called woronin bodies are anchored in proximity to the pore. this is a prominent example for precise spatial positioning of organelles, but so far the underlying molecular organization has remained largely unknown. using the pathogenic mould aspergillus fumiga ...201323869404
a case-based discussion on a patient with non-otogenic fungal skull base osteomyelitis: pitfalls in diagnosis.to discuss the diagnostic pitfalls and limitations of imaging investigations in non-otogenic skull base osteomyelitis.201323866727
understanding jejunal hemorrhage syndrome.jejunal hemorrhage syndrome (jhs) is an acute, highly fatal enterotoxemic disorder in dairy cattle that has been reported during the last few decades. no specific cause of this syndrome has been identified; however, several studies have revealed a strong association between jhs and infection with clostridium perfringens type a. a common mold, aspergillus fumigatus, has also been implicated as a potential causative agent in this disease syndrome. clinical signs of jhs (including sudden decreases ...201323865877
tlr5 stop codon polymorphism is associated with invasive aspergillosis after allogeneic stem cell transplantation.single nucleotide polymorphisms (snps) have been associated with an increased incidence of invasive aspergillosis (ia) after allogeneic stem cell transplantation (allo-sct). we analyzed 41 patients with proven/probable ia after allo-sct for an association of snps, within the tlr2, tlr4, tlr5, tlr9, and nod2/card15 genes, with susceptibility to ia. the control group consisted of 130 patients who had allo-sct but did not develop ia. while no association was found for donor snps and the recipients' ...201323862689
binary and ternary copper(ii) complexes of a tridentate ons ligand derived from 2-aminochromone-3 carboxaldehyde and thiosemicarbazide: synthesis, spectral studies and antimicrobial activity.a tridentate ons donor ligand, hl, was synthesized by the condensation of 2-aminochromone-3-carboxaldehyde with thiosemicarbazide. the structure of the ligand was elucidated by elemental analyses, ir, (1)h and (13)c nmr, electronic and mass spectra. reaction of the ligand with several copper(ii) salts, including aco(-), no3(-), so4(2-), cl(-), br(-) and clo4(-) afforded different metal complexes that reflect the non-coordinating or weakly coordinating power of the clo4(-) and br(-) anions as com ...201323860404
czech ethanol-free propolis extract displays inhibitory activity against a broad spectrum of bacterial and fungal pathogens.propolis acts primarily as a biocide against invasive bacteria and fungi in the hive, suggesting its potential for industrial applications. in food application, propolis is considered as a chemical preservative in meat products, extending shelf life of frozen meat and other food. the mechanism of action is still unclear due to the synergy of multiple compounds contained in propolis and due to parallel targeting of multiple pathways within each affected organism. here, we examined the antimicrobi ...201323915150
pharmacokinetics of posaconazole within epithelial cells and fungi: insights into potential mechanisms of action during treatment and prophylaxis.the antifungal posaconazole concentrates within host cells and protects against aspergillus fumigatus. the specific subcellular location of posaconazole and the mechanism by which cell-associated posaconazole inhibits fungal growth remain uncharacterized.201323908482
olfm4 deletion enhances defense against staphylococcus aureus in chronic granulomatous disease.chronic granulomatous disease (cgd) patients have recurrent life-threatening bacterial and fungal infections. olfactomedin 4 (olfm4) is a neutrophil granule protein that negatively regulates host defense against bacterial infection. the goal of this study was to evaluate the impact of olfm4 deletion on host defense against staphylococcus aureus and aspergillus fumigatus in a murine x-linked gp91phox-deficiency cgd model. we found that intracellular killing and in vivo clearance of s. aureus, as ...201323908114
aspergillosis sinusitis with cranio-orbital spread in an apparently immunocompetent patient.intracranial fungal infections are unusual and typically described in immunocompromised hosts. the authors describe a rare case of an immunocompetent white man presenting with blindness after aspergillus fumigatus infection of the ethmoidal air sinus with spread to the orbital apex and the frontal lobe. this was successfully treated by surgical drainage via a frontal craniotomy and long-term antifungal therapy with voriconazole.201323907857
the microbial colonization profile of respiratory devices and the significance of the role of disinfection: a blinded study.approximately 10-40% of all the nosocomial infections are pulmonary, which lead to grave complications. elderly, debilitated, or critically ill patients are at a high risk. the respiratory care equipments which include ventilators, humidifiers, nebulizers may have been identified as the potential vehicles which cause major nosocomial infections if they are colonized by fungi or bacteria.201323905094
new untargeted metabolic profiling combining mass spectrometry and isotopic labeling: application on aspergillus fumigatus grown on wheat.characterization of fungal secondary metabolomes has become a challenge due to the industrial applications of many of these molecules, and also due to the emergence of fungal threats to public health and natural ecosystems. given that, the aim of the present study was to develop an untargeted method to analyze fungal secondary metabolomes by combining high-accuracy mass spectrometry and double isotopic labeling of fungal metabolomes. the strain nrrl 35693 of aspergillus fumigatus , an important ...201323901908
synthesis and antifungal activities of miltefosine analogs.miltefosine is an alkylphosphocholine that shows broad-spectrum in vitro antifungal activities and limited in vivo efficacy in mouse models of cryptococcosis. to further explore the potential of this class of compounds for the treatment of systemic mycoses, nine analogs (3a-3i) were synthesized by modifying the choline structural moiety and the alkyl chain length of miltefosine. in vitro testing of these compounds against the opportunistic fungal pathogens candida albicans, candida glabrata, can ...201323891181
elimination of aspergillus fumigatus conidia from the airways of mice with allergic airway inflammation.aspergillus fumigatus conidia can exacerbate asthma symptoms. phagocytosis of conidia is a principal component of the host antifungal defense. we investigated whether allergic airway inflammation (aai) affects the ability of phagocytic cells in the airways to internalize the resting fungal spores.201323890251
typing clinical and animal environment aspergillus fumigatus gliotoxin producer strains isolated from brazil by pcr-rflp markers.aspergillus fumigatus, a well-known human and animal pathogen causing aspergillosis, has been historically identified by morphological and microscopic features. however, recent studies have shown that species identification on the basis of morphology alone is problematic. the aim of this work was to confirm the taxonomic state at specie level of a set of clinical (human and animal) and animal environment a. fumigatus strains identified by morphological criteria applying a pcr-rflp assay by an in ...201323889550
allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria.allergic bronchopulmonary aspergillosis (abpa) is an immunological pulmonary disorder caused by hypersensitivity to aspergillus fumigatus, manifesting with poorly controlled asthma, recurrent pulmonary infiltrates and bronchiectasis. there are estimated to be in excess of four million patients affected world-wide. the importance of recognizing abpa relates to the improvement of patient symptoms, and delay in development or prevention of bronchiectasis, one manifestation of permanent lung damage ...201323889240
deletion of the sec4 homolog srga from aspergillus fumigatus is associated with an impaired stress response, attenuated virulence and phenotypic heterogeneity.small gtpases of the rab family are master regulators of membrane trafficking, responsible for coordinating the sorting, packaging and delivery of membrane-bound vesicles to specific sites within eukaryotic cells. the contribution of these proteins to the biology of the human pathogenic fungus aspergillus fumigatus has not been explored. in this study, we characterized the srga gene, encoding a rab gtpase closely related to sec4. we found that a gfp-srga fusion protein accumulated preferentially ...201323785510
kb425796-a, a novel antifungal antibiotic produced by paenibacillus sp. 530603.the novel antifungal macrocyclic lipopeptidolactone, kb425796-a (1), was isolated from the fermentation broth of bacterial strain 530603, which was identified as a new paenibacillus species based on morphological and physiological characteristics, and 16s rrna sequences. kb425796-a (1) was isolated as white powder by solvent extraction, hp-20 and ods-b column chromatography, and lyophilization, and was determined to have the molecular formula c79h115n19o18. kb425796-a (1) showed antifungal activ ...201323778117
identification of ten kb425796-a congeners from paenibacillus sp. 530603 using an antifungal assay against aspergillus fumigatus in combination with micafungin.the discovery and characterization of natural congeners is one approach for understanding the relationship between chemical structure and biological function. we recently isolated the novel antifungal metabolite kb425796-a produced by the recently isolated bacterium paenibacillus sp. 530603. on the basis of morphological changes of aspergillus fumigatus induced by kb425796-a in combination with micafungin, we developed a highly sensitive screening method for the specific detection of kb425796-a ...201323778114
early diagnosis of cerebral aspergillosis with various methods: a case report.the clinical and laboratory diagnosis of cerebral aspergillosis (ca) is problematic and mortality is quite high, even in cases receiving appropriate treatment. therefore, an early and accurate diagnosis may prove to be life saving in patients with the diagnosis of ca. in this report, a case of ca which developed in a pediatric patient with acute lymphoblastic leukemia (all) is presented. upon development of neutropenia and focal seizures in the left arm during implementation of the all treatment ...201323774978
extraction optimization and bioactivity of polysaccharides from aspergillus fumigatus af1.aspergillus fumigatus was used to produce polysaccharide using sodium hydroxide pretreated rice straw as the sole carbon source by submerged fermentation. response surface methodology (rsm) was used to optimize the extraction of polysaccharide from the mycelia of a. fumigatus (paf). a three-level, three-factor box-behnken design (bbd) was applied for experimental design and analyzed the results to obtain the optimal extraction parameters. rsm analysis indicated good correspondence between experi ...201323768581
chemical composition and antimicrobial activity of the essential oils from four ruta species growing in algeria.antimicrobial properties of plants essential oils have been investigated in order to suggest them as potential tools to overcome the microbial drug resistance and the increasing incidence of food borne diseases problems. the aim of this research is to study the antibacterial and antifungal effects of four traditional plants essential oils, ruta angustifolia, ruta chalepensis, ruta graveolens and ruta tuberculata, against standard bacterial and fungal strains. the chemical compounds of the oils w ...201323768355
preliminary laboratory report of fungal infections associated with contaminated methylprednisolone injections.in september 2012, the centers for disease control and prevention (cdc) initiated an outbreak investigation of fungal infections linked to injection of contaminated methylprednisolone acetate (mpa). between 2 october 2012 and 14 february 2013, the cdc laboratory received 799 fungal isolates or human specimens, including cerebrospinal fluid (csf), synovial fluid, and abscess tissue, from 469 case patients in 19 states. a novel broad-range pcr assay and dna sequencing were used to evaluate these s ...201323761142
extrinsic extracellular dna leads to biofilm formation and colocalizes with matrix polysaccharides in the human pathogenic fungus aspergillus fumigatus.the environmentally acquired fungal pathogen aspergillus fumigatus causes a variety of severe diseases. furthermore, it is often found colonizing the respiratory tract of patients suffering from cystic fibrosis. conidia of this filamentous fungus adhere to substrate surfaces and germinate to form biofilms comprised of dense hyphal networks embedded in an adhesive extracellular matrix (ecm), built predominantly of polysaccharides. these fungal microconsortia are likely to be of clinical relevance ...201323760756
subunit architecture of the golgi dsc e3 ligase required for sterol regulatory element-binding protein (srebp) cleavage in fission yeast.the membrane-bound sterol regulatory element-binding protein (srebp) transcription factors regulate lipogenesis in mammalian cells and are activated through sequential cleavage by the golgi-localized site-1 and site-2 proteases. the mechanism of fission yeast srebp cleavage is less well defined and, in contrast, requires the golgi-localized dsc e3 ligase complex. the dsc e3 ligase consists of five integral membrane subunits, dsc1 through dsc5, and resembles membrane e3 ligases that function in e ...201323760507
cytokine and transcription factor expression by aspergillus fumigatus-stimulated peripheral blood mononuclear cells in dogs with sino-nasal aspergillosis.the causal agent of sino-nasal aspergillosis is usually aspergillus fumigatus, which is a saprophytic and ubiquitous fungus that causes a severe rhinosinusitis in apparent healthy dogs. affected dogs do not have systemic immuno-suppression. it has been shown previously that dogs affected by this disease have local over-expression of interleukin (il)-10 and th1 cytokines in nasal mucosal tissue. the aim of the present study was to assess the response of peripheral blood mononuclear cells (pbmc) f ...201323759303
discovery of cryptic polyketide metabolites from dermatophytes using heterologous expression in aspergillus nidulans.dermatophytes belonging to the trichophyton and arthroderma genera cause skin infections in humans and animals. from genome sequencing data, we mined a conserved gene cluster among dermatophytes that are homologous to one that produces an immunosuppressive polyketide in aspergillus fumigatus. using a recombination-based cloning strategy in yeast, we constructed fungal heterologous expression vectors that encode the cryptic clusters. when integrated into the model aspergillus nidulans host, a str ...201323758576
synergistic antifungal activity of kb425796-c in combination with micafungin against aspergillus fumigatus and its efficacy in murine infection models.kb425796-c is a novel antifungal metabolite produced by the newly isolated bacterial strain paenibacillus sp. no. 530603. this compound is a 40-membered macrocyclic lipopeptidolactone consisting of 12 amino acids and a 3-hydroxy-15-methylpalmitoyl moiety. kb425796-c displayed antifungal activity against micafungin-resistant fungi and was fungicidal to trichosporon asahii in vitro. in a murine systemic infection model of t. asahii, kb425796-c showed excellent efficacy upon i.p. administration at ...201323756682
genetic and structural validation of aspergillus fumigatus udp-n-acetylglucosamine pyrophosphorylase as an antifungal target.the sugar nucleotide udp-n-acetylglucosamine (udp-glcnac) is an essential metabolite in both prokaryotes and eukaryotes. in fungi, it is the precursor for the synthesis of chitin, an essential component of the fungal cell wall. udp-n-acetylglucosamine pyrophosphorylase (uap) is the final enzyme in eukaryotic udp-glcnac biosynthesis, converting utp and n-acetylglucosamine-1-phosphate (glcnac-1p) to udp-glcnac. as such, this enzyme may provide an attractive target against pathogenic fungi. here, w ...201323750903
allergic bronchopulmonary aspergillosis: a clinico-serological correlation with radiologic profile.to study the different types of radiological presentations of abpa in a tertiary clinic in northern india and analyze them with respect to serological profile and clinical characteristics.201323745673
synthesis, spectroscopic studies, molecular modeling and antimicrobial activity of binuclear co(ii) and cu(ii) complexes of 4,6-diacetylresorcinol.reactions of 4,6-diacetylresorcinol with different cobalt(ii) and copper(ii) salts viz., oac(-), cl(-), no3(-) and so4(2-), yielded a new series of binuclear metal complexes. reactions of the ligand with these metal ions in the presence of a secondary ligand (l') [o,o-donor; acetylacetone, n,o-donor; 8-hydroxyquinoline or n,n-donor; 1,10-phenanthroline and n,n,n',n'-tetramethylethylenediamine] in 1:2:2 (l:m:l') molar ratio yielded mixed-ligand complexes with different molar ratios. the metal com ...201323743042
cell wall perturbation sensitizes fungi to the antimalarial drug chloroquine.chloroquine (cq) has been a mainstay of antimalarial drug treatment for several decades. additional therapeutic actions of cq have been described, including some reports of fungal inhibition. here we investigated the action of cq in fungi, including the yeast model saccharomyces cerevisiae. a genomewide yeast deletion strain collection was screened against cq, revealing that bck1δ and slt2δ mutants of the cell wall integrity pathway are cq hypersensitive. this phenotype was rescued with sorbitol ...201323733464
quaternized n-substituted carboxymethyl chitosan derivatives as antimicrobial agents.introduction of quaternary ammonium moieties into n-substituted carboxymethyl chitosan (n-substituted cmch) derivatives enhances their biological activity. several derivatives of cmch having a variety of n-aryl substituents bearing either electron-donating or electron withdrawing groups have been synthesized by the reaction between amino group of cmch with various aromatic aldehydes under acidic conditions, followed by reduction of the produced schiff base derivatives with sodium cyanoborohydrid ...201323732327
structural requirements for sterol regulatory element-binding protein (srebp) cleavage in fission yeast.sterol regulatory element-binding proteins (srebps) are central regulators of cellular lipid synthesis and homeostasis. mammalian srebps are proteolytically activated and liberated from the membrane by golgi site-1 and site-2 proteases. fission yeast srebps, sre1 and sre2, employ a different mechanism that genetically requires the golgi dsc e3 ligase complex for cleavage activation. here, we established sre2 as a model to define structural requirements for srebp cleavage. we showed that sre2 cle ...201323729666
novel immunologic classification of aspergillosis in adult cystic fibrosis.patients with cystic fibrosis (cf) demonstrate a wide range of hypersensitivity responses to aspergillus, beyond allergic bronchopulmonary aspergillosis, which require classification.201323726262
corticosteroids block autophagy protein recruitment in aspergillus fumigatus phagosomes via targeting dectin-1/syk kinase signaling.aspergillus fumigatus is the predominant airborne fungal pathogen in immunocompromised patients. genetic defects in nadph oxidase (chronic granulomatous disease [cgd]) and corticosteroid-induced immunosupression lead to impaired killing of a. fumigatus and unique susceptibility to invasive aspergillosis via incompletely characterized mechanisms. recent studies link tlr activation with phagosome maturation via the engagement of autophagy proteins. in this study, we found that infection of human m ...201323817424
ficolin-1-ptx3 complex formation promotes clearance of altered self-cells and modulates il-8 production.the long pentraxin 3 (ptx3) has been shown to be important in maintaining internal tissue homeostasis and in protecting against fungal aspergillus fumigatus infection. however, the molecular mechanisms of how these functions are elicited are poorly delineated. ficolin-1 is a soluble pattern recognition molecule that interacts with ptx3. we hypothesized that heterocomplexes between ficolin-1 and ptx3 might mediate the signals necessary for sequestration of altered self-cells and a. fumigatus. we ...201323817411
a novel model of invasive fungal rhinosinusitis in rats.invasive fungal rhinosinusitis (ifrs) is a life-threatening inflammatory disease that affects immunocompromised patients, but animal models of the disease are scarce. this study aimed to develop an ifrs model in neutropenic rats.201323816783
a model for treating avian aspergillosis: serum and lung tissue kinetics for japanese quail (coturnix japonica) following single and multiple aerosol exposures of a nanoparticulate itraconazole suspension.aspergillosis is frequently reported in parrots, falcons and other birds held in captivity. inhalation is the main route of infection for aspergillus fumigatus, resulting in both acute and chronic disease conditions. itraconazole (itra) is an antifungal commonly used in birds, but administration requires repeated oral dosing and the safety margin is narrow. we describe lung tissue and serum pharmacokinetics of a nanoparticulate itra suspension administered to japanese quail by aerosol exposure. ...201323815436
regional cytokine responses to pulmonary aspergillosis in immunocompetent rats.rat models of pulmonary aspergillosis are used widely in diagnostic studies and in exploring antifungal therapeutic modalities, but there is lack of data concerning antifungal immunity in rats. in this study, cytokine response to pulmonary infection to aspergillus fumigatus in non-immunosuppressed rats is explored. temporal display (from the start of infection up to its eradication) of proinflammatory cytokines (ifn-γ and il-17) as well as th2/anti-inflammatory ones (il-4 and il-10) was explored ...201323810257
il-33-responsive innate lymphoid cells are an important source of il-13 in chronic rhinosinusitis with nasal polyps.chronic rhinosinusitis (crs) without nasal polyps (crssnp) and crs with nasal polyps (crswnp) are associated with th1 and th2 cytokine polarization, respectively; however, the pathophysiology of crs remains unclear. the importance of innate lymphoid cells in th2-mediated inflammatory disease has not been clearly defined.201323805875
tie2-dependent vhl knockdown promotes airway microvascular regeneration and attenuates invasive growth of aspergillus fumigatus.microvascular ischemia and infections are associated with the development of chronic rejection following lung transplantation. the von hippel–lindau protein (vhl) controls protein levels of hypoxia-inducible factors (hifs), regulates vascular repair, and improves tissue perfusion. here, we studied the role of vhl in microvascular repair by orthotopically transplanting tracheas into mice with vhl haplodeficiency in tie2 lineage cells. we showed that vhl haplodeficiency prolonged airway microvascu ...201323797537
efficacy of amphotericin b at suboptimal dose combined with voriconazole in a murine model of aspergillus fumigatus infection with poor in vivo response to the azole.the combination of amphotericin b at a suboptimal dose (0.3 mg/kg) with voriconazole has shown efficacy in prolonging survival and reducing tissue burden in a murine model of disseminated infection by an isolate of aspergillus fumigatus that had showed a poor in vivo response to the azole. the efficacy of the combined treatment was higher than that obtained with amphotericin b at 0.8 mg/kg.201323796928
functional analysis of an atp-binding cassette transporter protein from aspergillus fumigatus by heterologous expression in saccharomyces cerevisiae.aspergillus fumigatus is the major filamentous fungal pathogen in humans. although a. fumigatus can be treated with many of the available antifungal drugs, including azole compounds, drug resistant isolates are being recovered at an increasing rate. in other fungal pathogens such as the candida species, atp-binding cassette (abc) transporter proteins play important roles in development of clinically-significant azole resistance phenotypes. central among these abc transporter proteins are homolog ...201323796749
synthesis, structure and antifungal activity of thiophene-2,3-dicarboxaldehyde bis(thiosemicarbazone) and nickel(ii), copper(ii) and cadmium(ii) complexes: unsymmetrical coordination mode of nickel complex.the reaction of nickel(ii), copper(ii) chlorides and cadmium(ii) chloride and bromide with thiophene-2,3-dicarboxaldehyde bis(thiosemicarbazone) (2,3btstch2) leads to a series of new complexes: [ni(2,3btstch)]cl, [cu(2,3btstc)], [cdcl2(2,3btstch2)] and [cdbr2(2,3btstch2)]. the crystal structures of the ligand and of [ni(2,3btstch)]cl complex have been determined. in this case, we remark an unusual non-symmetrical coordination mode for the two functional groups: one acting as a thione and the sec ...201323792913
amphotericin b- and voriconazole-echinocandin combinations against aspergillus spp.: effect of serum on inhibitory and fungicidal interactions.antifungal combination therapy with voriconazole or amphotericin b and an echinocandin is often employed as primary or salvage therapy for management particularly of refractory aspergillosis. the pharmacodynamic interactions of amphotericin b- and voriconazole-based combinations with the three echinocandins caspofungin, micafungin, and anidulafungin in the presence of serum were tested against 15 aspergillus fumigatus complex, a. flavus complex, and a. terreus complex isolates to assess both the ...201323856768
[fungal and bacterial contamination of 30 general practitioners' consultation room in franche-comté (eastern france)].to evaluate the level of microbial contamination of general pratice environment.201323856447
targeting iron acquisition blocks infection with the fungal pathogens aspergillus fumigatus and fusarium oxysporum.filamentous fungi are an important cause of pulmonary and systemic morbidity and mortality, and also cause corneal blindness and visual impairment worldwide. utilizing in vitro neutrophil killing assays and a model of fungal infection of the cornea, we demonstrated that dectin-1 dependent il-6 production regulates expression of iron chelators, heme and siderophore binding proteins and hepcidin in infected mice. in addition, we show that human neutrophils synthesize lipocalin-1, which sequesters ...201323853581
from bench to bedside: preclinical evaluation of a self-inactivating gammaretroviral vector for the gene therapy of x-linked chronic granulomatous disease.chronic granulomatous disease (cgd) is a primary immunodeficiency characterized by impaired antimicrobial activity in phagocytic cells. as a monogenic disease affecting the hematopoietic system, cgd is amenable to gene therapy. indeed in a phase i/ii clinical trial, we demonstrated a transient resolution of bacterial and fungal infections. however, the therapeutic benefit was compromised by the occurrence of clonal dominance and malignant transformation demanding alternative vectors with equal e ...201323845071
genetic and structural validation of aspergillus fumigatus n-acetylphosphoglucosamine mutase as an antifungal target.aspergillus fumigatus is the causative agent of ia (invasive aspergillosis) in immunocompromised patients. it possesses a cell wall composed of chitin, glucan and galactomannan, polymeric carbohydrates synthesized by processive glycosyltransferases from intracellular sugar nucleotide donors. here we demonstrate that a. fumigatus possesses an active afagm1 (a. fumigatus n-acetylphosphoglucosamine mutase), a key enzyme in the biosynthesis of udp (uridine diphosphate)-glcnac (n-acetylglucosamine), ...201323844980
aspergillus fumigatus hyphal damage caused by noninvasive radiofrequency field-induced hyperthermia.we studied the effect of noninvasive radiofrequency-induced hyperthermia on the viability of aspergillus fumigatus hyphae in vitro. radiofrequency-induced hyperthermia resulted in significant (>70%, p < 0.0001) hyphal damage in a time and thermal dose-dependent fashion as assessed by xtt [(sodium 2,3,-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl] (1)-2h-tetrazolium inner salt)], dibac [bis-(1,3-dibutylbarbituric acid) trimethine oxonol] staining, and transmission electron micro ...201323836166
occupational allergic respiratory diseases in garbage workers: relevance of molds and actinomycetes.exposures to molds and bacteria (especially actinomycetes) at workplaces are common in garbage workers, but allergic respiratory diseases due to these microorganisms have been described rarely. the aim of our study was a detailed analysis of mold or bacteria-associated occupational respiratory diseases in garbage workers. from 2002 to 2011 four cases of occupational respiratory diseases related to garbage handling were identified in our institute (ipa). hypersensitivity pneumonitis (hp) was diag ...201323835992
imaging living cells surface and quantifying its properties at high resolution using afm in qi™ mode.since the last 10 years, afm has become a powerful tool to study biological samples. however, the classical modes offered (imaging or tapping mode) often damage sample that are too soft or loosely immobilized. if imaging and mechanical properties are required, it requests long recording time as two different experiments must be conducted independently. in this study we compare the new qi™ mode against contact imaging mode and force volume mode, and we point out its benefit in the new challenges ...201323522742
assessment of aspergillus fumigatus pathogenicity in aerosol-challenged chickens (gallus gallus) belonging to two lineages.infection due to the mold aspergillus fumigatus remains a common and life-threatening infection in many animals, especially birds. animal models are still required to better understand the physiopathology of infection and evaluate diagnostic tools and treatment procedures. the aim of the present study was to assess the pathogenicity of a. fumigatus in two lineages of chicken (gallus gallus): spf white leghorn pa12 layers and conventional ja657 broilers. four-day-old birds were experimentally inf ...201323522612
intravenous antibiotics reduce the presence of aspergillus in adult cystic fibrosis sputum.pseudomonas aeruginosa and aspergillus fumigatus frequently co-colonise the airways of patients with cystic fibrosis (cf). this study aimed to assess the impact of short-term administration of intravenous antipseudomonal antibiotics during cf exacerbations on the presence of aspergillus.201323513028
monocyte- and macrophage-targeted nadph oxidase mediates antifungal host defense and regulation of acute inflammation in mice.chronic granulomatous disease, an inherited disorder of the nadph oxidase in which phagocytes are defective in the generation of superoxide anion and downstream reactive oxidant species, is characterized by severe bacterial and fungal infections and excessive inflammation. although nadph oxidase isoforms exist in several lineages, reactive oxidant generation is greatest in neutrophils, where nadph oxidase has been deemed vital for pathogen killing. in contrast, the function and importance of nad ...201323509361
sun proteins belong to a novel family of β-(1,3)-glucan-modifying enzymes involved in fungal morphogenesis.sun proteins are involved in yeast morphogenesis, but their function is unknown.201323508952
csp typing of chinese aspergillus fumigatus isolates: identification of additional csp types.cell surface protein (csp) typing is a typing strategy that employs comparative dna sequence analysis of the 12-mer tandem repeat region of the afua_3g08890 gene. the csp typing scheme and modified nomenclature was applied to a collection of 162 clinical aspergillus fumigatus isolates from china. a total of 16 csp variants were observed, including five that were newly reported, indicating that phylogeographic differences may exist between the chinese and the previously studied australian, europe ...201323506321
novel terephthaloyl thiourea cross-linked chitosan hydrogels as antibacterial and antifungal agents.four novel terephthaloyl thiourea chitosan (ttu-chitosan) hydrogels were synthesized via a cross-linking reaction of chitosan with different concentrations of terephthaloyl diisothiocyanate. their structures were investigated by elemental analyses, ftir, sem and x-ray diffraction. the antimicrobial activities of the hydrogels against three species of bacteria (bacillis subtilis, staphylococcus aureus and escherichia coli) and three crop-threatening pathogenic fungi (aspergillus fumigatus, geotri ...201323500435
liver transplantation in cystic fibrosis: a report from baylor college of medicine and the texas children's hospital.cf affects one of 2000 caucasians, and approximately 25% are found to have cfld for which olt may be indicated. timing of transplantation, contraindications, and survival are still widely debated. we report the outcomes of olt for pediatric patients with cfld from the largest children's hospital in the united states. our records since september 1998 were analyzed for all patients undergoing olt for cfld. nine patients were then compared to similar patients in the unos/optn database (n = 155). su ...201323489441
the fumagillin biosynthetic gene cluster in aspergillus fumigatus encodes a cryptic terpene cyclase involved in the formation of β-trans-bergamotene.fumagillin 1 is a meroterpenoid from aspergillus fumigatus that is known for its anti-angiogenic activity by binding to human methionine aminopeptidase 2. the genetic and molecular basis for biosynthesis of 1 had been an enigma despite the availability of the a. fumigatus genome sequence. here, we report the identification and verification of the fma gene cluster, followed by characterization of the polyketide synthase and acyltransferase involved in biosynthesis of the dioic acid portion of 1. ...201323488861
chloroquine modulates the fungal immune response in phagocytic cells from patients with chronic granulomatous disease.invasive aspergillosis is a major threat to patients with chronic granulomatous disease (cgd). fungal pathogenesis is the result of a diminished antifungal capacity and dysregulated inflammation. a deficient nadph-oxidase complex results in defective phagolysosomal alkalization. to investigate the contribution of defective ph regulation in phagocytes among patients with cgd during fungal pathogenesis, we evaluated the effect of the acidotropic, antimalarial drug chloroquine (cq) on the antifunga ...201323482646
identification and evaluation of novel acetolactate synthase inhibitors as antifungal agents.high-throughput phenotypic screening against the yeast saccharomyces cerevisiae revealed a series of triazolopyrimidine-sulfonamide compounds with broad-spectrum antifungal activity, no significant cytotoxicity, and low protein binding. to elucidate the target of this series, we have applied a chemogenomic profiling approach using the s. cerevisiae deletion collection. all compounds of the series yielded highly similar profiles that suggested acetolactate synthase (ilv2p, which catalyzes the fir ...201323478965
role of ficolin-a and lectin complement pathway in the innate defense against pathogenic aspergillus species.aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. we have shown that the complement component ficolin-a significantly binds to aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by n-acetylglucosamine and n-acetylgalacto ...201323478320
proteolytic cleavage of the long pentraxin ptx3 in the airways of cystic fibrosis patients.the prototypic long pentraxin ptx3, a soluble pattern recognition receptor, plays an important role in innate defense against selected pathogens by favoring their elimination and the initiation of protective responses. ptx3 has notably beneficial effects in mice infected with aspergillus fumigatus and pseudomonas aeruginosa. cystic fibrosis (cf), a severe inherited autosomal recessive disease, is characterized by recurrent lung infections, especially by these two pathogens. we thus hypothesized ...201323475792
gliotoxinogenic aspergillus fumigatus in the dairy herd environment.the potential association between hygienic conditions in the environment of lactating cows and the presence of gliotoxinogenic aspergillus fumigatus strains was studied. milk samples (individual cow's milk [icm], bulk tank milk [btm]) from 44 dairy farms were sampled. in icm samples, eight different species of aspergillus were identified. a. flavus and a. fumigatus were predominant, with 37.8% and 26.1% relative densities, respectively. a. fumigatus strains were isolated from 61.4% of the btm sa ...201323467846
the tell-tale heart: aspergillus fumigatus endocarditis in an immunocompetent patient.aspergillus is a saprophytic, spore-forming fungus that is ubiquitous in our daily environment. inhalation of the airborne conidia leads to a variety of diseases, from asymptomatic colonization to disseminated disease. immunocompromised patients are usually viewed as the population most susceptible to aspergillosis because of their lack of host immune defenses. however, a healthy immune system does not preclude an individual from susceptibility to aspergillosis. our case illustrates an immunocom ...201323466974
azole resistance in aspergillus fumigatus from bronchoalveolar lavage fluid samples of patients with chronic diseases.triazole resistance in aspergillus fumigatus has been increasing. we explored the a. fumigatus azole resistance profiles in bronchoalveolar lavage (bal) fluid samples from danish patients examined for aspergillosis.201323463213
epidemiology of invasive fungal infections in the intensive care unit: results of a multicenter italian survey (aurora project).the aims of this study are to evaluate the epidemiology of invasive fungal infections (ifis) in patients admitted to an intensive care unit (icu) in southern italy and the in vitro antifungal susceptibility of isolates.201323463186
dectin-1 expression at early period of aspergillus fumigatus infection in rat's corneal epithelium.to investigate the expression of dendritic cell-associated c-type lectin-1(dectin-1) at the early period of aspergillus fumigatus infection in rat's corneal epithelium.201323447102
vitamin d regulation of ox40 ligand in immune responses to aspergillus fumigatus.ox40 ligand (ox40l) is a costimulatory molecule involved in th2 allergic responses. it has been shown that vitamin d deficiency is associated with increased ox40l expression in peripheral cd11c(+) cells and controls th2 responses to aspergillus fumigatus in vitro in cystic fibrosis (cf) patients with allergic bronchopulmonary aspergillosis (abpa). to investigate if vitamin d deficiency regulated ox40l and th2 responses in vivo, we examined the effect of nutritional vitamin d deficiency on costim ...201323439304
partial reconstruction of the ergot alkaloid pathway by heterologous gene expression in aspergillus nidulans.ergot alkaloids are pharmaceutically and agriculturally important secondary metabolites produced by several species of fungi. ergot alkaloid pathways vary among different fungal lineages, but the pathway intermediate chanoclavine-i is evolutionarily conserved among ergot alkaloid producers. at least four genes, dmaw, easf, ease, and easc, are necessary for pathway steps prior to chanoclavine-i; however, the sufficiency of these genes for chanoclavine-i synthesis has not been established. a fragm ...201323435153
receptor-mediated signaling in aspergillus fumigatus.aspergillus fumigatus is the most pathogenic species among the aspergilli, and the major fungal agent of human pulmonary infection. to prosper in diverse ecological niches, aspergilli have evolved numerous mechanisms for adaptive gene regulation, some of which are also crucial for mammalian infection. among the molecules which govern such responses, integral membrane receptors are thought to be the most amenable to therapeutic modulation. this is due to the localization of these molecular sensor ...201323430083
fungal cell wall organization and biosynthesis.the composition and organization of the cell walls from saccharomyces cerevisiae, candida albicans, aspergillus fumigatus, schizosaccharomyces pombe, neurospora crassa, and cryptococcus neoformans are compared and contrasted. these cell walls contain chitin, chitosan, β-1,3-glucan, β-1,6-glucan, mixed β-1,3-/β-1,4-glucan, α-1,3-glucan, melanin, and glycoproteins as major constituents. a comparison of these cell walls shows that there is a great deal of variability in fungal cell wall composition ...201323419716
cr(iii), mn(ii), fe(iii), co(ii), ni(ii), cu(ii) and zn(ii) new complexes of 5-aminosalicylic acid: spectroscopic, thermal characterization and biological activity studies.the complexing behavior of mesalazine (5-aminosalicylic acid; 5-asa) towards the transition metal ions namely, cr(iii), mn(ii), fe(iii), co(ii), ni(ii), cu(ii) and zn(ii) have been examined by elemental analyses, magnetic measurements, electronic, ir and (1)h nmr. thermal properties and decomposition kinetics of all complexes are investigated. the interpretation, mathematical analyses and evaluation of kinetic parameters of all thermal decomposition stages have been evaluated using coats-redfern ...201323416903
frequency, diagnosis and management of fungal respiratory infections.this review highlights key recent advances in fungal respiratory infections, encompassing developments in epidemiology, diagnostics and management, focussing on aspergillus, pneumocystis and cryptococcus as key pathogens.201323411576
investigation of aspergillus fumigatus biofilm formation by various "omics" approaches.in the lung, aspergillus fumigatus usually forms a dense colony of filaments embedded in a polymeric extracellular matrix called biofilm (bf). this extracellular matrix embeds and glues hyphae together and protects the fungus from an outside hostile environment. this extracellular matrix is absent in fungal colonies grown under classical liquid shake conditions (pl), which were historically used to understand a. fumigatus pathobiology. recent works have shown that the fungus in this aerial grown ...201323407341
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