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microbiology of the upper and lower airways in pediatric cystic fibrosis patients.objective to evaluate the microbiology of the upper and lower airways in pediatric cystic fibrosis (cf) patients who underwent sinus surgery. study design retrospective case series with chart review. setting tertiary care children's hospital. subjects and methods a total of 201 paired sinus and pulmonary cultures from 105 cf patients were identified between 1996 and 2014. demographics and culture results were analyzed. results the mean age of patients was 11.2 ± 5.4 years (range, 1-27 years), an ...201728440108
co-colonisation with aspergillus fumigatus and pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: an irish registry analysis.pulmonary infection is the main cause of death in cystic fibrosis (cf). aspergillus fumigatus (af) and pseudomonas aeruginosa (pa) are the most prevalent fungal and bacterial pathogens isolated from the cf airway, respectively. our aim was to determine the effect of different colonisation profiles of af and pa on the clinical status of patients with cf.201728431569
characterization of the rax1 gene encoding a putative regulator of g protein signaling in aspergillus fumigatus.the filamentous fungus aspergillus fumigatus is the major cause of life threatening invasive aspergillosis, and its small hydrophobic asexual spores (conidia) are the major infection agent. to better understand biology of a. fumigatus, we have characterized the rax1 gene encoding a putative regulator of g protein signaling (rgs). the deletion (δ) of rax1 results in restricted colony growth and highly reduced number of conidia in a. fumigatus. transcript levels of the three central activators of ...201728427940
filamentous fungal carbon catabolite repression supports metabolic plasticity and stress responses essential for disease progression.aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. while many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. we propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. to th ...201728423062
in vivo efficacy of liposomal amphotericin b against wild-type and azole-resistant aspergillus fumigatus isolates in two different immunosuppression models of invasive aspergillosis.using an immunocompetent murine model of invasive aspergillosis (ia), we previously reported that the efficacy of liposomal amphotericin b (l-amb) (ambisome) is not hampered by the presence of azole resistance mutations in aspergillus fumigatus (s. seyedmousavi, w. j. g. melchers, j. w. mouton, and p. e. verweij, antimicrob agents chemother 57:1866-1871, 2013, https://doi.org/10.1128/aac.02226-12). we here investigated the role of immune suppression, i.e., neutropenia and steroid treatment, in l ...201728416540
insights from the genome of a high alkaline cellulase producing aspergillus fumigatus strain obtained from peruvian amazon rainforest.here, we report the complete genome sequence of a high alkaline cellulase producing aspergillus fumigatus strain lmb-35aa isolated from soil of peruvian amazon rainforest. the genome is ∼27.5mb in size, comprises of 228 scaffolds with an average gc content of 50%, and is predicted to contain a total of 8660 protein-coding genes. of which, 6156 are with known function; it codes for 607 putative cazymes families potentially involved in carbohydrate metabolism. several important cellulose degrading ...201728412514
successful treatment of azole-resistant invasive aspergillosis in a bottlenose dolphin with high-dose posaconazole.invasive aspergillosis due to azole-resistant aspergillus fumigatus is difficult to manage. we describe a case of azole-resistant invasive aspergillosis in a female bottlenose dolphin, who failed to respond to voriconazole and posaconazole therapy. as intravenous therapy was precluded, high dose posaconazole was initiated aimed at achieving trough levels exceeding 3 mg/l. posaconazole serum levels of 3-9.5 mg/l were achieved without significant side-effects. follow-up bronchoscopy and computed t ...201728409094
[the clinical characteristics of 17 cases of primary ciliary dyskinesia].objective: to review the clinical data of cases of primary ciliary dyskinesia (pcd), and to explore the clinical characteristics for the understanding of pcd. methods: we retrospectively summarized 17 patients with pcd diagnosed in peking union medical college hospital from jan 2009 to dec 2014. there were 7 male and 10 female patients, with the age from 6 to 57 years at the time of diagnosis. the mean onset age of the disease was 11.7±2.1 years, and the mean age at diagnosis was 29.5±3.5 years. ...201728395407
a dsrna virus with filamentous viral particles.viruses with double-stranded rna genomes form isometric particles or are capsidless. here we report a double-stranded rna virus, colletotrichum camelliae filamentous virus 1 (ccfv-1) isolated from a fungal pathogen, that forms filamentous particles. ccfv-1 has eight genomic double-stranded rnas, ranging from 990 to 2444 bp, encoding 10 putative open reading frames, of which open reading frame 1 encodes an rna-dependent rna polymerase and open reading frame 4 a capsid protein. when inoculated, th ...201728761042
pharmacokinetics of azole antifungals in cystic fibrosis.defects in mucociliary clearance predispose cystic fibrosis (cf) patients to airway colonization and infection by various fungi, especially aspergillus fumigatus. although the clinical significance of airway fungal colonization is not clear, several studies have suggested its association with worsening lung function and increased risk of cf exacerbations. antifungal triazole agents have been used in cf patients with airway fungal colonization or infections with varying results. limited pharmacok ...201728795298
role of ergothioneine in microbial physiology and pathogenesis.l-ergothioneine is synthesized in actinomycetes, cyanobacteria, methylobacteria and some fungi. in contrast to other low molecular weight redox buffers, glutathione and mycothiol, ergothioneine is primarily present as a thione rather than a thiol at physiological ph, which makes it resistant to autoxidation. ergothioneine regulates microbial physiology and enables survival of the microbes under stressful conditions encountered in their natural environments. in particular, ergothioneine enables p ...201728791878
[the expression of triggering receptor expressed on myeloid cells receptor-1 in aspergillus infected mice].objective: to investigate the expression of triggering receptor expressed on myeloid cells receptor-1 (trem-1) in plasma and bronchoalveolar lavage fluid (balf) and its correlation with galactomannan, ifnγ, il-6 and il-10 in aspergillus infected mice. methods: cyclophosphamide(ctx) was intraperitoneally injected and fumigatus spore suspension was inhaled by nose to establish the immunocompromised invasive pulmonary aspergillosis(ipa) mouse model.healthy controls, immunocompromised only and ipa o ...201728789494
in vitro antifungal, probiotic, and antioxidant functional properties of a novel lactobacillus paraplantarum isolated from fermented dates in saudi arabia.fermented foods produced using dates are used in gulf countries as beneficial and healthful foods. the beneficial microbial flora in fermented dates contributes to maintaining the nutritional properties of dates by preventing the growth of spoilage fungi. here, we examined the antifungal, probiotic, and antioxidant properties of the novel lactobacillus strain d-3 isolated from fermented dates.201728480570
bioremoval of arsenic (v) from aqueous solutions by chemically modified fungal biomass.the biosorption of arsenic (v) on nine chemically modified biomasses (with iron oxide coated) of mycelia fungi: aspergillus flavus iii, iv and v, aspergillus fumigatus i-ii, paecilomyces sp., cladosporium sp., mucor sp-1 and 2 was studied in this work. this study provides evidence that the biomasses of the fungi a. flavus, iv, iii and v, paecilomyces sp., and a. fumigatus i were very efficient at removing 1 mg/l of the metal in solution, using atomic absorption spectroscopy (aas), achieving the ...201728681286
single tracheal inoculation of aspergillus fumigatus conidia induced aspergillosis in juvenile falcons (falco spp.).aspergillosis is a common and life-threatening respiratory disease in raptors with acute and chronic courses. among raptors, gyrfalcons (falco rusticolus) and their hybrids are often declared to be highly susceptible with juvenile individuals being the most susceptible. however, species- and age-specific experimental studies are lacking and minimal infective doses (ids) for aspergillus spp. conidia are unknown.therefore, 8-week-old, healthy gyr-hybrid falcons (f. rusticolus x f. cherrug) (n = 18 ...201728758799
hypertonic saline as a useful tool for sputum induction and pathogen detection in cystic fibrosis.the aim of this study was to compare the qualitative and semi-quantitative detection of pathogens in the airway secretions of patients with cystic fibrosis (cf) and the sputum induction capacity before and after inhalation of 7% hypertonic saline solution (hss).201728455785
antimicrobial activity, toxicity and anti-inflammatory potential of methanolic extracts of four ethnomedicinal plant species from punjab, pakistan.the plant species aristolochia indica (ai), melilotus indicus (mi), tribulus terrestris (tt) and cuscuta pedicellata (cp) are widely used in folk medicine in the villages around chowk azam, south punjab, pakistan. the aim of this study was to evaluate the antioxidant activity, phytochemical composition, and the antibacterial, antifungal, cytotoxic and anti-inflammatory potential of the four medicinal plants listed above. for cp stem, this study represents (to the best of our knowledge) the first ...201728595608
the in vitro effects of interferon-gamma, alone or in combination with amphotericin b, tested against the pathogenic fungi candida albicans and aspergillus fumigatus.recent studies into the antifungal activity of nk-cells against the aspergillus fumigatus have presented differing accounts on their mode of antifungal activity. one of these mechanisms proposed that nk-cells may kill the fungus via the direct effects of exposure to interferon gamma (ifn-γ).201728764751
characteristics of meningitis following transsphenoidal endoscopic surgery: a case series and a systematic literature review.meningitis occurs in 0.8-1.5% of patients undergoing neurosurgery. the aim of the study was to evaluate the characteristics of meningitis after endoscopic endonasal transsphenoidal surgery (eets) comparing the findings retrieved to those highlighted by literature search.201728776163
adamts-13 regulates neutrophil recruitment in a mouse model of invasive pulmonary aspergillosis.von willebrand factor (vwf) is secreted as an acute phase protein during inflammation. adamts-13 regulates the size and prothrombotic activity of vwf by it's specific proteolytic activity. to determine the relevance of this regulatory pathway for the innate inflammatory response by polymorphonuclear neutrophils (pmn), we employed a mouse model of invasive pulmonary aspergillosis (ipa) where pmn functionality is crucial for fungal clearance and survival. ipa was induced by intratracheal applicati ...201728775254
pulmonary and sinus fungal diseases in non-immunocompromised patients.the human respiratory tract is exposed daily to airborne fungi, fungal enzymes, and secondary metabolites. the endemic fungi histoplasma capsulatum, coccidioides spp, blastomyces dermatitidis, and paracoccidioides brasiliensis, and occasionally aspergillus fumigatus, are primary pulmonary pathogens of otherwise healthy people. such infections resolve in most people, and only a few infections lead to disease. however, many fungi are directly allergenic by colonising the respiratory tract or indir ...201728774699
recovery of metallo-tolerant and antibiotic resistant psychrophilic bacteria from siachen glacier, pakistan.cultureable bacterial diversity of previously unexplored siachen glacier, pakistan, was studied. out of 50 isolates 33 (66%) were gram negative and 17 (34%) gram positive. about half of the isolates were pigment producers and were able to grow at 4-37°c. 16s rrna gene sequences revealed gram negative bacteria dominated by proteobacteria (especially γ-proteobacteria and β-proteobacteria) and flavobacteria. the genus pseudomonas (51.51%, 17) was dominant among γ- proteobacteria. β-proteobacteria c ...201728746396
cytological diagnosis of primary cutaneous aspergillosis masquerading as lipoma in a known case of lepromatous leprosy.primary cutaneous aspergillosis is a rare disease, caused by organisms like aspergillus flavus and aspergillus fumigatus. fine needle aspiration cytology (fnac) is a simple and well established tool for the diagnosis of mycotic infections. we report a case of forearm swelling that presented clinically as lipoma in a known case of lepromatous leprosy. it was diagnosed as primary cutaneous aspergillosis on fnac, which was subsequently confirmed on culture. cutaneous aspergillosis co-existing with ...201728658789
effects of ε-polylysine on pseudomonas aeruginosa and aspergillus fumigatus biofilm in vitro.background the antimicrobial mechanisms of ε-polylysine (epl) against pseudomonas aeruginosa and aspergillus fumigatus biofilm were investigated. material and methods we assessed the changes in electric conductivity of broth and total sugar concentration, as well as changes in phosphorous metabolism and protein expression, of the 2 organisms before and after treatment with epl. results the experimental results showed that epl has antimicrobial activity against pseudomonas aeruginosa and aspergil ...201728863128
serum aspergillus fumigatus-specific igg antibody decreases after antifungal treatment in chronic pulmonary aspergillosis patients. 201728862383
the role of multispecies social interactions in shaping pseudomonas aeruginosa pathogenicity in the cystic fibrosis lung.pseudomonas aeruginosa is a major pathogen in the lungs of cystic fibrosis (cf) patients. however, it is now recognised that a diverse microbial community exists in the airways comprising aerobic and anaerobic bacteria as well as fungi and viruses. this rich soup of microorganisms provides ample opportunity for interspecies interactions, particularly when considering secreted compounds. here, we discuss how p. aeruginosa-secreted products can have community-wide effects, with the potential to ul ...201728859314
myba, a new player driving survival of the conidium of the human pathogen aspergillus fumigatus.aspergillus fumigatus is an opportunistic human pathogen that causes various complications in patients with a weakened immune system functions. asexual spores of a. fumigatus are responsible for initiation of aspergillosis. long-term viability and proper germination of dormant conidia depend on trehalose accumulation, which protect the spores against thermal and oxidative stress. a putative myb transcription factor, myba has been recently found to be responsible for a variety of physiological an ...201728840304
aspergillus fumigatus protein phosphatase ppza is involved in iron assimilation, secondary metabolite production, and virulence.metal restriction imposed by mammalian hosts during an infection is a common mechanism of defence to reduce or avoid the pathogen infection. metals are essential for organism survival due to its involvement in several biological processes. aspergillus fumigatus causes invasive aspergillosis, a disease that typically manifests in immunocompromised patients. a. fumigatus ppza, the catalytic subunit of protein phosphatase z (ppz), has been recently identified as associated with iron assimilation. a ...201728753224
a comparative study on the activity of fungal lytic polysaccharide monooxygenases for the depolymerization of cellulose in soybean spent flakes.lytic polysaccharide monooxygenases (lpmos) are copper-dependent enzymes capable of the oxidative breakdown of polysaccharides. they are of industrial interest due to their ability to enhance the enzymatic depolymerization of recalcitrant substrates by glycoside hydrolases. in this paper, twenty-four lytic polysaccharide monooxygenases (lpmos) expressed in trichoderma reesei were evaluated for their ability to oxidize the complex polysaccharides in soybean spent flakes, an abundant and industria ...201728750348
pharmacodynamics of the orotomides against aspergillus fumigatus: new opportunities for treatment of multidrug-resistant fungal disease.f901318 is an antifungal agent with a novel mechanism of action and potent activity against aspergillus spp. an understanding of the pharmacodynamics (pd) of f901318 is required for selection of effective regimens for study in phase ii and iii clinical trials. neutropenic murine and rabbit models of invasive pulmonary aspergillosis were used. the primary pd endpoint was serum galactomannan. the relationships between drug exposure and the impacts of dose fractionation on galactomannan, survival, ...201728830945
ergot alkaloids contribute to virulence in an insect model of invasive aspergillosis.neosartorya fumigata (aspergillus fumigatus) is the most common cause of invasive aspergillosis, a frequently fatal lung disease primarily affecting immunocompromised individuals. this opportunistic fungal pathogen produces several classes of specialised metabolites including products of a branch of the ergot alkaloid pathway called fumigaclavines. the biosynthesis of the n. fumigata ergot alkaloids and their relation to those produced by alternate pathway branches in fungi from the plant-inhabi ...201728827626
chronic pulmonary aspergillosis as a cause of smear-negative tb and/or tb treatment failure in nigerians.to evaluate chronic pulmonary aspergillosis (cpa) as an alternative diagnosis of smear-negative tuberculosis (tb) and treatment failure in tb patients in nigeria.201728826456
sniffing out the hypoxia volatile metabolic signature of aspergillus fumigatus.invasive aspergillosis (ia) is a life-threatening infectious disease caused by fungi from the genus aspergillus, with an associated mortality as high as 90% in certain populations. ia-associated pulmonary lesions are characteristically depleted in oxygen relative to normal lung tissue, and it has been shown that the most common causal agent of ia, aspergillus fumigatus, must respond to low-oxygen environments for pathogenesis and disease progression. previous studies have demonstrated marked alt ...201728825403
aspergillus bronchitis in patients with cystic fibrosis.aspergillus fumigatus frequently colonizes the airways of patients with cystic fibrosis (cf) and may cause various severe infections, such as bronchitis. serological data, sputum dependent markers and longitudinal data of treated cases of aspergillus bronchitis were evaluated for further description of this infection. this study, which comprises three substudies, aimed to analyze epidemiological data of aspergillus in cf and the entity of aspergillus bronchitis. in a first step, data of the germ ...201728819878
molecular diagnosis of invasive aspergillosis and detection of azole resistance by a newly commercialized pcr kit.aspergillus fumigatus is the main species responsible for aspergillosis in humans. the diagnosis of aspergillosis remains difficult, and the rapid emergence of azole resistance in a. fumigatus, is worrisome. the aim of this study was to validate the new mycogenie® a. fumigatus real-time pcr kit and to evaluate its performance in clinical samples for the detection of a. fumigatus and its azole resistance. this multiplex assay detects dna from the a. fumigatus species complex by targeting the 28s- ...201728814586
proteomic profiling of the antifungal drug response of aspergillus fumigatus to voriconazole.antifungal resistance is an emerging problem and one of the reasons for treatment failure of invasive aspergillosis (ia). voriconazole has become a standard therapeutic for the treatment of this often fatal infection. we studied the differentially expressed proteins as a response of aspergillus fumigatus to voriconazole by employing the two-dimensional difference gel electrophoresis (dige) technique. due to addition of drug, a total of 135 differentially synthesized proteins were identified by m ...201728811086
aspergillus endophthalmitis resulting in development of retinal aspergilloma.a 78-year-old immunocompetent man presented with a 3-month history of painless decreased vision and panuveitis with a macular lesion presumed to be due to endogenous endophthalmitis. he had been treated with systemic, intravenous, and intravitreal antibiotics and antifungal agents as well as intravitreal steroids. a culture from a prior vitrectomy had grown a single colony of aspergillus thought to be a contaminant. the macular lesion enlarged and caused a tractional retinal detachment. the pati ...201728810046
spatial patterns and impacts of environmental and climatic factors on canine sinonasal aspergillosis in northern california.sinonasal aspergillosis (sna) causes chronic nasal discharge in dogs and has a worldwide distribution, although most reports of sna in north america originate from the western usa. sna is mainly caused by aspergillus fumigatus, a ubiquitous saprophytic filamentous fungus. infection is thought to follow inhalation of spores. sna is a disease of the nasal cavity and/or sinuses with variable degrees of local invasion and destruction. while some host factors appear to predispose to sna (such as belo ...201728717638
coupling the pretreatment and hydrolysis of lignocellulosic biomass by the expression of beta-xylosidases.thermochemical pretreatment and enzymatic hydrolysis are the areas contributing most to the operational costs of second generation ethanol in lignocellulosic biorefineries. the improvement of lignocellulosic enzyme cocktails has been significant in the recent years. although the needs for the reduction of the energy intensity and chemical consumption in the pretreatment step are well known, the reduction of the severity of the process strongly affects the enzymatic hydrolysis yield. to explore t ...201728710860
allergic bronchopulmonary mycosis due to exposure to eurotium herbariorum after the great east japan earthquake.indoor mold levels typically increase after natural disasters, flooding, and water damage. eurotium herbariorum is the sexual stage of aspergillus glaucus. case presentation a 66-year-old, japanese male, ex-smoker had been diagnosed with bronchial asthma when he was five years old; he achieved remission at the age of 13 years. he was displaced from his home during the great east japan earthquake on march 11, 2011 and moved to temporary housing in miyagi prefecture in june 2011. he experienced th ...201728807087
abridged version of the awmf guideline for the medical clinical diagnostics of indoor mould exposure: s2k guideline of the german society of hygiene, environmental medicine and preventive medicine (ghup) in collaboration with the german association of allergists (aeda), the german society of dermatology (ddg), the german society for allergology and clinical immunology (dgaki), the german society for occupational and environmental medicine (dgaum), the german society for hospital hygiene (dgkh), the german society for pneumology and respiratory medicine (dgp), the german mycological society (dmykg), the society for pediatric allergology and environmental medicine (gpa), the german federal association of pediatric pneumology (bapp), and the austrian society for medical mycology (ögmm).this article is an abridged version of the awmf mould guideline "medical clinical diagnostics of indoor mould exposure" presented in april 2016 by the german society of hygiene, environmental medicine and preventive medicine (gesellschaft für hygiene, umweltmedizin und präventivmedizin, ghup), in collaboration with the above-mentioned scientific medical societies, german and austrian societies, medical associations and experts. indoor mould growth is a potential health risk, even if a quantitati ...201728804700
cu-sensing transcription factor mac1 coordinates with the ctr transporter family to regulate cu acquisition and virulence in aspergillus fumigatus.copper (cu) is an essential trace element and is regarded as an important virulence factor in fungal pathogens. previous studies suggest that a putative cu-sensing transcription factor mac1 and the cu transporter ctr family play important roles during fungal development and virulence. however, how cu importers of the ctr family are involved in the cu acquisition and what is the functional relationship between them have not been fully investigated yet. here, we demonstrate that the yeast mac1 hom ...201728803907
successful long-term extracorporeal membrane oxygenation for invasive pulmonary aspergillosis: a case report.extracorporeal membrane oxygenation is an established life-saving procedure for severe acute respiratory failure due to various causes. in general, the duration of extracorporeal membrane oxygenation ranges from 1 to 2 weeks, with withdrawal recommended if no improvement is noted. we report a successful case of long-term extracorporeal membrane oxygenation management for respiratory failure due to invasive pulmonary aspergillus infection.201728797271
intra- and inter-individual variability of aspergillus fumigatus reactive t-cell frequencies in healthy volunteers in dependency of mould exposure in residential and working environment.invasive aspergillosis remains a deadly disease in immunocompromised patients, whereas the combination of an exaggerated immune response and continuous exposure lead to various hyperinflammatory diseases. this pilot study aimed to gain an overview of the intra- and inter-individual variability in aspergillus fumigatus reactive t-helper cells in healthy adults and the correlation with environmental mould exposure. in this flow cytometric study, the frequencies of cd154(+) a. fumigatus reactive t ...201728786508
crocin reduces a. fumigatus-induced airway inflammation and nf-κb signal activation.chronic obstructive pulmonary disease (copd) is a chronic airway inflammation and its exacerbation is often accompanied by a. aspergillus infection. increasing evidences demonstrated the potent antioxidant and anti-inflammatory effects of crocin. however, the role of crocin in a. aspergillus-induced inflammation is still unknown. we aimed to evaluate the role of crocin in inflammation response induced by a. aspergillus in human bronchial epithelial cells and the possible mechanisms. beas-2b and ...201728786504
small colony variants of pseudomonas aeruginosa display heterogeneity in inhibiting aspergillus fumigatus biofilm.pseudomonas aeruginosa and aspergillus fumigatus are major microbes in cystic fibrosis (cf). we reported non-mucoid p. aeruginosa isolates more inhibitory to a. fumigatus than mucoid ones. another cf p. aeruginosa phenotype, small colony variants (scvs), is an unknown factor in intermicrobial competition with a. fumigatus. clinical scv isolates and reference cf non-mucoid isolate (pa10, producing normal-sized colonies) were compared. live cells of p. aeruginosa or filtrates from p. aeruginosa pl ...201728785939
postsurgical mediastinal aspergilloma masquerading as malignancy.a 70-year-old man with non-ischaemic dilated cardiomyopathy presented with symptoms of fatigue, chills and unintentional weight loss over the past 2 months. initial evaluation revealed anaemia, peripheral leucocytosis and elevated inflammatory markers. results of an oesophagogastroduodenoscopy, colonoscopy, blood bacterial and fungal cultures and bone marrow biopsy were negative. an (18)f-fdg positron-emission tomography-ct demonstrated an indeterminate, intensely fdg-avid 5 cm × 2 cm × 5.6 cm × ...201728784902
il-33 signaling regulates innate il-17a and il-22 production via suppression of prostaglandin e2 during lung fungal infection.members of the il-1 family play protective and regulatory roles in immune defense against the opportunistic mold aspergillus fumigatus in this study, we investigated the il-1 family member il-33 in lung defense against a. fumigatus il-33 was detected in the naive lung, which further increased after exposure to a. fumigatus in a dectin-1-independent manner. mice deficient in the receptor for il-33 (il1rl1(-/-)) unexpectedly demonstrated enhanced lung clearance of a. fumigatus il-33 functioned as ...201728784844
clinical and microbiological characteristics of pantoea agglomerans infection in children.pantoea agglomerans is an environmental gram-negative bacterium that rarely is responsible for the infections in humans but it is often a causative factor of a number of occupational diseases. this study evaluated the clinical and microbiological characteristics and pathogenicity of p. agglomerans in children. we retrospectively reviewed microbiological test results for all children (1 month old to 18 years old) who were admitted to our pediatric hospital between january 2000 to june 2015 and ha ...201728780309
the global problem of antifungal resistance: prevalence, mechanisms, and management.all serious fungal infections need appropriate antifungal therapy for successful patient outcome. only a few classes of antifungal drugs are available, so the emergence of resistance to single drug classes and now multidrug resistance greatly hampers patient management. azole resistance among candida and aspergillus species is one of the greatest challenges to clinical success, followed by echinocandin and multidrug resistance among some candida species, especially candida glabrata. the spread o ...201728774698
fungal pathogens in cf airways: leave or treat?chronic airway infection plays an essential role in the progress of cystic fibrosis (cf) lung disease. in the past decades, mainly bacterial pathogens, such as pseudomonas aeruginosa, have been the focus of researchers and clinicians. however, fungi are frequently detected in cf airways and there is an increasing body of evidence that fungal pathogens might play a role in cf lung disease. several studies have shown an association of fungi, particularly aspergillus fumigatus and candida albicans, ...201728770417
fatal mycotic aneurysm of the basilar artery caused by aspergillus fumigatus in a patient with pituitary adenoma and meningitis.fungal infections of the central nervous system (cns) frequently occur in immunosuppressed patients. here, we describe the case of an immunocompetent 64-year-old man who presented with diplopia, right-sided hemiparesis, and a mild headache after cleaning and replacing nesting boxes of wild birds during the preceding months. lumbar puncture revealed pleocytosis, elevated protein, and lactate levels in the cerebrospinal fluid (csf). initial imaging showed ischemia in the left thalamus and an enlar ...201728770205
simultaneous primary invasive cutaneous aspergillosis in two preterm twins: case report and review of the literature.primary invasive cutaneous aspergillosis is a rare fungal infection that occurs mostly in immunocompromised patients. newborns of very low birth weight present a high risk for this type of infection due to an immaturity of the cutaneous barrier and of the immune system.201728768499
filamentous fungal human pathogens from food emphasising aspergillus, fusarium and mucor.disease caused by filamentous fungal human pathogens (ffhp) is increasing. these organisms cause severe mycoses in immunosuppressed individuals, such as those: (a) with aids; (b) having undergone transplantation; and/or (c) undergoing chemotherapy. immunocompetent people can become infected. some ffhp are isolated from foods which may be fomites. however, the information concerning particular species on specific food is large, dispersed and difficult to obtain. reports of filamentous fungi from ...201728767050
caspofungin-mediated growth inhibition and paradoxical growth in aspergillus fumigatus involve fungicidal hyphal tip lysis coupled with regenerative intrahyphal growth and dynamic changes in β-1,3-glucan synthase localization.caspofungin targets cell wall β-1,3-glucan synthesis and is guideline-recommended to treat invasive aspergillosis as salvage therapy. although caspofungin is inhibitory at low concentrations, it exhibits a 'paradoxical effect' (reversal of growth inhibition) at high concentrations by an undetermined mechanism. treatment with either growth inhibitory (0.5 μg/ml) or paradoxical growth-inducing (4 μg/ml) caspofungin concentrations for 24 h caused similar abnormalities, including wider, hyperbranche ...201728760907
toward the standardization of mycological examination of sputum samples in cystic fibrosis: results from a french multicenter prospective study.fungal respiratory colonization of cystic fibrosis (cf) patients emerges as a new concern; however, the heterogeneity of mycological protocols limits investigations. we first aimed at setting up an efficient standardized protocol for mycological analysis of cf sputa that was assessed during a prospective, multicenter study: "mucofong" program (phrc-06/1902). sputa from 243 cf patients from seven centers in france were collected over a 15-month period and submitted to a standardized protocol base ...201728748285
dual induction of new microbial secondary metabolites by fungal bacterial co-cultivation.the frequent re-isolation of known compounds is one of the major challenges in drug discovery. many biosynthetic genes are not expressed under standard culture conditions, thus limiting the chemical diversity of microbial compounds that can be obtained through fermentation. on the other hand, the competition during co-cultivation of two or more different microorganisms in most cases leads to an enhanced production of constitutively present compounds or an accumulation of cryptic compounds that a ...201728744271
structural and in vivo studies on trehalose-6-phosphate synthase from pathogenic fungi provide insights into its catalytic mechanism, biological necessity, and potential for novel antifungal drug design.the disaccharide trehalose is critical to the survival of pathogenic fungi in their human host. trehalose-6-phosphate synthase (tps1) catalyzes the first step of trehalose biosynthesis in fungi. here, we report the first structures of eukaryotic tps1s in complex with substrates or substrate analogues. the overall structures of tps1 from candida albicans and aspergillus fumigatus are essentially identical and reveal n- and c-terminal rossmann fold domains that form the glucose-6-phosphate and udp ...201728743811
enzymatic mechanisms involved in evasion of fungi to the oxidative stress: focus on scedosporium apiospermum.the airways of patients with cystic fibrosis (cf) are frequently colonized by various filamentous fungi, mainly aspergillus fumigatus and scedosporium species. to establish within the respiratory tract and cause an infection, these opportunistic fungi express pathogenic factors allowing adherence to the host tissues, uptake of extracellular iron, or evasion to the host immune response. during the colonization process, inhaled conidia and the subsequent hyphae are exposed to reactive oxygen speci ...201728639066
phytochemical screening, antimicrobial and cytotoxicity studies of ethanol leaf extract of aphaniasenegalensis (sapindaceae).aphania senegalensis (sapindaceae) is commonly used in senegalese traditional medicine to treat pain, inflammation, asthenia, bacterial and fungal infections. the aim of this study was to determine the type of phytochemical constituents present in the ethanol leaf extract and its antimicrobial activity against selected bacterial and fungal pathogens.201728638876
azole resistance in aspergillus fumigatus: a consequence of antifungal use in agriculture?agricultural industry uses pesticides to optimize food production for the growing human population. a major issue for crops is fungal phytopathogens, which are treated mainly with azole fungicides. azoles are also the main medical treatment in the management of aspergillus diseases caused by ubiquitous fungi, such as aspergillus fumigatus. however, epidemiological research demonstrated an increasing prevalence of azole-resistant strains in a. fumigatus. the main resistance mechanism is a combina ...201728638374
antifungal activity against filamentous fungi of ts1, a multifunctional toxin from tityus serrulatus scorpion venom.antimicrobial peptides (amps) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. the search for new amps has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. in this work, we evaluate the effects of tityus serrulatus venom (tsv), its fractions and its major toxin ts1, a beta-neurotoxin, on fungi growth. the fractions were obtained by ion-exchange chromatography ...201728634472
progressive dispersion of azole resistance in aspergillus fumigatus: fatal invasive aspergillosis in a patient with acute myeloid leukemia infected with an a. fumigatus strain with a cyp51a tr46 y121f m172i t289a allele.patients with hematologic malignancies as well as allogeneic hematopoietic stem cell transplantation (hsct) patients are at high risk for invasive aspergillosis. here, we report a culture- and autopsy-proven fatal invasive aspergillosis in an allogeneic hstc patient which he developed despite posaconazole prophylaxis. the agent was determined to be an azole-resistant aspergillus fumigatus strain bearing the cyp51a mutation combination tr46 y121f m172i t289a. at increasing frequency, the azole re ...201728743702
addition of 17-(allylamino)-17-demethoxygeldanamycin to a suboptimal caspofungin treatment regimen in neutropenic rats with invasive pulmonary aspergillosis delays the time to death but does not enhance the overall therapeutic efficacy.caspofungin (cas) which is used as salvage therapy in patients with invasive pulmonary aspergillosis (ipa) inhibits the 1,3-β-d-glucan synthesis in aspergillus fumigatus. inhibiting 1,3-β-d-glucan synthesis induces a stress response and in an invertebrate model it was demonstrated that inhibiting this response with geldamycin enhanced the therapeutic efficacy of cas. since geldamycin itself is toxic to mammalians, the therapeutic efficacy of combining geldamycin with cas was not studied in roden ...201728742113
in vivo biomarker analysis of the effects of intranasally dosed pc945, a novel antifungal triazole, on aspergillus fumigatus infection in immunocompromised mice.pc945 is a novel triazole optimized for lung delivery, and the objective of this study is to determine the effects of intranasally dosed pc945 on aspergillus fumigatus infection and associated biomarkers in immunocompromised mice. pc945, posaconazole, or voriconazole was administered intranasally once daily on days 0 to 3 (early intervention) or days 1 to 3 (late intervention) postinfection in temporarily neutropenic a/j mice infected intranasally with a. fumigatus, and bronchoalveolar lavage fl ...201728630185
synthesis, antimicrobial, antiquorum-sensing and antitumor activities of new benzimidazole analogs.new benzimidazole analogs were prepared and tested for antimicrobial efficacy toward escherichia coli atcc 12435, bacillus cereus uw 85, staphylococcus aureus atcc 29213, candida albicans and aspergillus fumigatus 293. results indicated that compound 10 has potent and broad spectrum antimicrobial activity. in addition, 4b and 5c showed eminent antimicrobial efficacy toward b. cereus, s. aureus, c. albicans and a. fumigatus. furthermore, 12 and 14 demonstrated interesting antifungal activity towa ...201728623814
evidence of unique genetic diversity in aspergillus fumigatus isolates from cameroon.aspergillus fumigatus is a saprophytic fungus that can cause lethal invasive aspergillosis in immunocompromised patients. recent studies have shown that eurasian and north american populations of a. fumigatus often consist of genetically diverse strains. however, very little is known about african populations of a. fumigatus. here, we characterise the genetic diversity and triazole susceptibility of a. fumigatus in cameroon, west africa. a total of 495 soil samples were obtained from nine collec ...201728730597
a nonredundant phosphopantetheinyl transferase, ppta, is a novel antifungal target that directs secondary metabolite, siderophore, and lysine biosynthesis in aspergillus fumigatus and is critical for pathogenicity.secondary metabolites are key mediators of virulence for many pathogens. aspergillus fumigatus produces a vast array of these bioactive molecules, the biosynthesis of which is catalyzed by nonribosomal peptide synthetases (nrpss) or polyketide synthases (pkss). both nrpss and pkss harbor carrier domains that are primed for acceptance of secondary metabolic building blocks by a phosphopantetheinyl transferase (p-pant). the a. fumigatus p-pant ppta has been shown to prime the putative nrps pes1 in ...201728720735
the binding mechanism between azoles and fgcyp51b, sterol 14α-demethylase of fusarium graminearum.fusarium graminearum is the main pathogen of fusarium head blight (fhb), a worldwide plant disease and one of the major wheat diseases in china. the control of the fhb is mainly dependent on the application of dmis fungicides. fungal sterol 14α-demethylase enzymes (cyp51) are the main target for dmis fungicides. in order to investigate the binding mechanism between azoles and cyp51b in f.graminearum, the molecular modeling study and biological evaluation were performed.201728719051
preparation of a trp-bodipy fluorogenic amino acid to label peptides for enhanced live-cell fluorescence imaging.fluorescent peptides are valuable tools for live-cell imaging because of the high specificity of peptide sequences for their biomolecular targets. when preparing fluorescent versions of peptides, labels must be introduced at appropriate positions in the sequences to provide suitable reporters while avoiding any impairment of the molecular recognition properties of the peptides. this protocol describes the preparation of the tryptophan (trp)-based fluorogenic amino acid fmoc-trp(c2-bodipy)-oh and ...201728703788
chemoenzymatic synthesis, nanotization, and anti-aspergillus activity of optically enriched fluconazole analogues.despite recent advances in diagnostic and therapeutic methods in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. one strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of candida antarctica lipase (cal) for the preparation of optically enriched fluconazole analogues. anti-aspergillus activity was observed for an optically enriched derivative, (-)-s-2-(2',4'-difl ...201728607028
drug sensitivity and resistance mechanism in aspergillus section nigri strains from japan.aspergillus niger and its related species, known as aspergillus section nigri, are ubiquitously distributed across the globe and are often isolated from clinical specimens. in japan, aspergillus section nigri is second most often isolated from clinical specimens following aspergillus fumigatus we determined the species of aspergillus section nigri isolated in japan by dna sequencing of partial β-tubulin genes and investigated drug susceptibility by the clsi m38-a2 method. the collection containe ...201728607016
gastroesophageal reflux disease and pulmonary diseases associated with aspergillosis: is there a connection?we studied the relationship between gord and allergic bronchopulmonary aspergillosis (abpa), chronic pulmonary aspergillosis (cpa), or aspergillus bronchitis.201728702854
the cell wall of the human fungal pathogen aspergillus fumigatus: biosynthesis, organization, immune response, and virulence.more than 90% of the cell wall of the filamentous fungus aspergillus fumigatus comprises polysaccharides. biosynthesis of the cell wall polysaccharides is under the control of three types of enzymes: transmembrane synthases, which are anchored to the plasma membrane and use nucleotide sugars as substrates, and cell wall-associated transglycosidases and glycosyl hydrolases, which are responsible for remodeling the de novo synthesized polysaccharides and establishing the three-dimensional structur ...201728701066
effects of intranasally dosed posaconazole on fungal load and biomarkers in aspergillus fumigatus infected immunocompromised mice.although anti-fungal triazoles are dosed orally or systemically for aspergillus fumigatus infection, systemic adverse events and limited exposure of the lung cavity would make a topical treatment for the lung an attractive option. in this study, we examined the effects of intranasally dosed posaconazole on survival rates and biomarkers in a. fumigatus (itraconazole susceptible: atcc13073 [af]; or resistant: ncpf7100 [afr]) infected, temporarily neutropenic a/j mice. once daily treatment produced ...201728699245
effects of aspergillus fumigatus on glucocorticoid receptor and β2-adrenergic receptor expression in a rat model of asthma.conventional inhaled corticosteroids or β2-adrenergic receptor agonists do not work well in some asthmatic populations while empirical antifungal therapy has obvious impact on those patients. the study was designed to investigate whether short-term exposure to aspergillus fumigatus (a. fumigatus) could decrease glucocorticoid receptor (gcr) and β2-adrenergic receptor (adrb2) expression in lung tissue of asthmatic rats.201728696809
combination therapy with isavuconazole and micafungin for treatment of experimental invasive pulmonary aspergillosis.invasive pulmonary aspergillosis (ipa) is an important cause of morbidity and mortality in immunocompromised patients. we hypothesized that simultaneous inhibition of biosynthesis of ergosterol in the fungal cell membrane and (1→3)-β-d-glucan in the cell wall, respectively, by the antifungal triazole isavuconazole (isa) and the echinocandin micafungin (mfg) may result in improved outcomes in experimental ipa in persistently neutropenic rabbits. treatments included isa at 20 mg/kg of body weight/ ...201728696236
cd4(+) t cells mediate aspergillosis vaccine protection.adaptive effector cd4(+) t cells play essential roles in the defense against fungal infections, especially against invasive aspergillosis (ia). such protective cd4(+) t cells can be generated through immunization with specialized antifungal vaccines, as has been demonstrated for pulmonary aspergillus fumigatus infections in mouse experiments. adaptive transfer of fungal antigen-specific cd4(+) t cells conferred protection onto non-immunized naive mice, an experimental approach that could potenti ...201728584997
precise and efficient in-frame integration of an exogenous gfp tag in aspergillus fumigatus by a crispr system.as one of the most common airborne fungal pathogenic species, aspergillus fumigatus infection is the increasingly fatal threat to immunocompromised patients worldwide. setting up an efficient live-cell pathogen-labeling system will give insight into the dynamic process of the pathogen invasion in host, which offers us opportunities to explore the pathogenesis of a. fumigatus. in this chapter, we have described an efficient crispr-cas9 system, which enables a precise in situ tag-insertion of an e ...201728584995
post-tuberculosis mycetoma: bronchoscopic removal.a 76-year-old male non-smoker presented to our institution with cough and haemoptysis. he had been treated for cavitatory pulmonary mycobacterium tuberculosis of the right upper lobe 10 years previously. chest radiograph and subsequent computed tomography (ct) of the chest demonstrated a right upper cavity containing a mass suspicious for mycetoma. flexible bronchoscopy under conscious sedation demonstrated a mass obstructing the anterior segment of the right upper lobe. the abnormality was subs ...201728580148
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