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isolation and identification of phyllospheric bacteria possessing antimicrobial activity from astragalus obtusifolius, prosopis juliflora, xanthium strumarium and hippocrepis unisiliqousa.the widespread utilization of antimicrobial compounds has caused emergence of resistant microorganisms in the world. hence, the research to probe the products with antimicrobial features has led to finding natural habitats and discovering new pharmaceutical products.201728090278
rna interference mediated knockdown of brugia malayi udp-galactopyranose mutase severely affects parasite viability, embryogenesis and in vivo development of infective larvae.galactofuranose is an essential cell surface component present in bacteria, fungi and several nematodes such as caenorhabditis spp., brugia spp., onchocerca spp. and strongyloides spp. this sugar maintains the integrity of parasite surface and is essential for virulence. udp-galactopyranose mutase (bmugm) plays a key role in galf biosynthesis by catalyzing conversion of udp-galactopyranose into udp-galactofuranose and knockout studies of the gene in leishmania major, mycobacterium and aspergillu ...201728103957
development of a dot-blot assay for the detection of mould-specific ige in the belgian population.data on mould sensitization in the general population are scarce and mostly on aspergillus fumigatus, alternaria alternata and cladosporium herbarum.201727878528
mould allergens: where do we stand with molecular allergy diagnostics?: part 13 of the series molecular allergology.the official who/iuis database (www.allergen.org) currently lists 77 mould allergens from a variety of protein families. to date, only eight recombinant single allergens from three mould species are available for molecular allergy diagnosis of mould sensitization. these include ralt a 1, the major allergen in alternaria alternata-sensitized individuals, and enolase ralt a 6 with it potential cross-reactivity to mould, food and natural latex allergens. rasp f 1, 2, 3, 4 and 6 from aspergillus fum ...201726120524
synthesis and antimicrobial properties of 4-acylaminobenzenethiosulfoacid s-esters.a series of esters of 4-acetyl, 4-trifluoroacetyl- and 4-(3-chloropropionyl)aminobenzenethiosulfoacids (twenty-four compounds) were synthesized and characterized by elemental analysis, (1)h nmr and ir spectroscopy. the antibacterial activity of the novel candidates has been screened using the agar diffusion or serial dilution methods against representative gram-positive (staphylococcus aureus, bacillus subtilis, bacillus mesentericus, mycobacterium sp., mycobacterium luteum), gram-negative (aero ...201728344478
establishment of crispr/cas9 in alternaria alternata.the filamentous fungus alternaria alternata is a potent producer of many secondary metabolites, some of which like alternariol or alternariol-methyl ether are toxic and/or cancerogenic. many alternaria species do not only cause post-harvest losses of food and feed, but are aggressive plant pathogens. despite the great economic importance and the large number of research groups working with the fungus, the molecular toolbox is rather underdeveloped. gene deletions often result in heterokaryotic s ...201728286319
biocontrol potential of halotolerant bacterial chitinase from high yielding novel bacillus pumilus mcb-7 autochthonous to mangrove ecosystem.the multifaceted role of chitinase in medicine, agriculture, environmental remediation and various other industries greatly demands the isolation of high yielding chitinase producing microorganisms with improved properties. the current study aimed to investigate the isolation, characterization and biocontrol prospective of chitinase producing bacterial strains autochthonous to the extreme conditions of mangrove ecosystems. among the 51 bacterial isolates screened, bacillus pumilus mcb-7 with hig ...201728364802
thermophilic fungi to dominate aflatoxigenic/mycotoxigenic fungi on food under global warming.certain filamentous fungi produce mycotoxins that contaminate food. mycotoxin contamination of crops is highly influenced by environmental conditions and is already affected by global warming, where there is a succession of mycotoxigenic fungi towards those that have higher optimal growth temperatures. aflatoxigenic fungi are at the highest limit of temperature although predicted increases in temperature are beyond that constraint. the present paper discusses what will succeed these fungi and re ...201728218685
matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for rapid identification of fungal rhinosinusitis pathogens.filamentous fungi are among the most important pathogens, causing fungal rhinosinusitis (frs). current laboratory diagnosis of frs pathogens mainly relies on phenotypic identification by culture and microscopic examination, which is time consuming and expertise dependent. although matrix-assisted laser desorption/ionization time-of-flight (maldi-tof) ms has been employed to identify various fungi, its efficacy in the identification of frs fungi is less clear.201728100314
high fungal spore burden with predominance of aspergillus in hospital air of a tertiary care hospital in chandigarh.the prevalence of fungal spores in the hospital air is essential to understand the hospital-acquired fungal infections. air conditioners (acs) used in hospitals may either reduce spores in air or be colonised by fungi and aid in its dissemination. the present study was conducted to assess the fungal spore burden in ac and non-ac areas. we found a high fungal spore count in air irrespective of whether the area was ac or non-ac. the most predominant species isolated were aspergillus flavus and asp ...201727934837
cuspidate a, new anti-fungal triterpenoid saponin from lepidagathis cuspidata.one new triterpenoid saponin named cuspidate a (1) along with a known oleanane-based triterpenoid saponin clemontanoside-c were isolated from the roots of lepidagathis cuspidata. the structure of new compound (1) was established after detailed analysis of spectroscopic data including 1d and 2d nmr spectra. this is the first report on clemontanoside-c from this genus. these saponins were found to be effective against the selected fungal strains aspergillus flavus, rhizopus stolinifer, penicillum ...201727827543
occupational exposure to fungi and particles in animal feed industry.very few studies regarding fungal and particulate matter (pm) exposure in feed industry have been reported, although such contaminants are likely to be a significant contributing factor to several symptoms reported among workers. the purpose of this study has been to characterize fungal and dust exposure in one portuguese feed industry.201727221292
septic arthritis due to tubercular and aspergillus co-infection.aspergillus septic arthritis is a rare and serious medical and surgical problem. it occurs mainly in immunocompromised patients. aspergillus fumigatus is the most common causative organism followed by aspergillus flavus. the most common site affected is knee followed by shoulder, ankle, wrist, hip and sacroiliac joint. debridement and voriconazole are primary treatment of articular aspergilosis. to the best of our knowledge, there are no reported cases of co-infection of tuberculosis (tb) and as ...201727293296
a prospective study of fungal biomarkers to improve management of invasive fungal diseases in a mixed specialty critical care unit.the diagnosis of invasive fungal diseases (ifd) in critical care patients (crcp) is difficult. the study investigated the performance of a set of biomarkers for diagnosis of ifd in a mixed specialty critical care unit (crcu).201728384600
molecular insights into pathogenesis and infection with aspergillus fumigatus.the virulence of fungi is dependent on multiple factors, including the immune status of patients and biological features of fungi. in particular, the virulence of aspergillus fumigatus is due to the complex interaction among various molecules involved in thermotolerance (such as ribosomal biogenesis proteins, α-mannosyltransferase and heat shock proteins), pigment production (dhn-melanin), immune evasion (like melanin and hydrophobin) and nutrient uptake (such as siderophores and zinc transporte ...201728381925
chronic granulomatous disease presenting as aspergillus fumigatus pneumonia in a previously healthy young woman.background chronic granulomatous disease (cgd) is a rare immunodeficiency disease caused by a genetic defect in the nadph (nicotinamide adenine dinucleotide phosphate) oxidase enzyme, resulting in increased susceptibility to bacterial and fungal infections. the inheritance can be x-linked or autosomal recessive. patients usually present with repeated infections early in life. we present an unusual case of a 23-year-old patient diagnosed with cgd. case report a 23-year-old white woman with no pre ...201728377567
between-laboratory analysis of igg antibodies against aspergillus fumigatus in paired quality control samples. 201728375842
clinical effectiveness of early posaconazole suspension pre-emptive therapy in lung transplant recipients: the alfred's experience.this study describes the clinical outcomes and therapeutic drug monitoring (tdm) following posaconazole suspension pre-emptive therapy in lung transplant (ltx) recipients.201728369489
inter-country transfer of triazole-resistant aspergillus fumigatus on plant bulbs.we investigated whether plants imported to ireland from the netherlands might harbor triazole-resistant aspergillus fumigatus. samples of plant bulbs were positive for triazole-resistant a. fumigatus with cyp51a mutations. we hypothesize that this represents a route for inter-country transfer of an emerging resistance mechanism in a major opportunistic mold pathogen.201728369271
functional investigation of iron-responsive microsomal proteins, including mirc, in aspergillus fumigatus.the functionality of many microsome-associated proteins which exhibit altered abundance in response to iron limitation in aspergillus fumigatus is unknown. here, we generate and characterize eight gene deletion strains, and of most significance reveal that mirc (afua_2g05730) contributes to the maintenance of intracellular siderophore [ferricrocin (fc)] levels, augments conidiation, confers protection against oxidative stress, exhibits an intracellular localization and contributes to fungal viru ...201728367141
a proteomic and ultrastructural characterization of aspergillus fumigatus' conidia adaptation at different culture ages.the airborne fungus aspergillus fumigatus is one of the most common agents of human fungal infections with a remarkable impact on public health. however, a. fumigatus conidia atmospheric resistance and longevity mechanisms are still unknown. therefore, in this work, the processes underlying conidial adaptation were studied by a time course evaluation of the proteomics and ultrastructural changes of a. fumigatus' conidia at three time-points selected according to relevant changes previously estab ...201728365406
apoptotic effect of demethoxyfumitremorgin c from marine fungus aspergillus fumigatus on pc3 human prostate cancer cells.demethoxyfumitremorgin c, a secondary metabolite of the marine fungus, aspergillus fumigatus, had been reported to demonstrate cytotoxic effect on mouse tsft210 cells. however, no information is available regarding its functional mechanism and the chemo-sensitization effects on different kinds of human cancer cells. we found that treatment of demethoxyfumitremorgin c inhibited the cell viability of pc3 human advanced prostate cancer cells, induced apoptosis as determined by annexin v/propidium i ...201728359723
azole-resistant aspergillus fumigatus harboring tr34/l98h, tr46/y121f/t289a and tr53 mutations related to flower fields in colombia.resistance to triazoles in aspergillus fumigatus has been reported in azole-naive patients in europe, asia, australia and north america. this resistance has been linked to fungicide-driven mutations in the cyp51a gene and its promoter region. we investigated the presence of environmental azole-resistant a. fumigatus strains related to the use of azole fungicides in colombia. soil samples were collected from flower beds, flower fields and public gardens from the outskirts, suburbs and city centre ...201728358115
effect of anaerobiasis or hypoxia on pseudomonas aeruginosa inhibition of aspergillus fumigatus biofilm.pseudomonas aeruginosa (pa) and aspergillus fumigatus (af) are the major bacterial and fungal pathogens in the airways of cystic fibrosis (cf) patients. this is likely related to their ability to form biofilms. both microbes have been associated with cf disease progression. the interplay between these two pathogens has been studied under aerobic conditions, though accumulating data indicates that much of the cf airway is hypoxic or anaerobic. we studied the microbial interaction in these latter ...201728357473
changes in the epidemiological landscape of invasive mould infections and disease.although a wide variety of pathogens are associated with invasive mould diseases, aspergillus spp. have historically been one of the most common causative organisms. most invasive mould infections are caused by members of the aspergillus fumigatus species complex and an emerging issue is the occurrence of azole resistance in a. fumigatus, with resistance to amphotericin b documented in other aspergillus spp. the epidemiology of invasive fungal disease has shifted in recent years as non-a. fumiga ...201728355462
innate lung defense during invasive aspergillosis: new mechanisms.invasive aspergillosis (ia) is one of the most difficult to treat and, consequently, one of the most lethal fungal infections known to man. continued use of immunosuppressive agents during chemotherapy and organ transplantation often leads to the development of neutropenia, the primary risk factor for ia. however, ia is also becoming more appreciated in chronic diseases associated with corticosteroid therapy. the innate immune response to aspergillus fumigatus, the primary agent in ia, plays a p ...201728231567
invasive pulmonary aspergillosis in an immunocompromised patient with severe ulcerative colitis.inflammatory bowel disease patients at risk of opportunistic infections are those treated with immunomodulators. toruner and colleagues found that corticosteroid use was more commonly associated with fungal infections. we present a case of invasive pulmonary aspergillosis due to corticosteroid therapy in the context of a severe ulcerative colitis flare. we want to highlight the relationship between aspergillus fumigatus and horses; and the use of leucocitapheresis combined with mesalazine as an ...201728229616
α-bisabolol inhibits aspergillus fumigatus af239 growth via affecting microsomal ∆(24)-sterol methyltransferase as a crucial enzyme in ergosterol biosynthesis pathway.finding new compounds with antifungal properties is an important task due to the side effects of common antifungal drugs and emerging antifungal resistance in fungal strains. ∆(24)-sterol methyltransferase (24-smt) is a crucial enzyme that plays important roles in fungal ergosterol biosynthesis pathway and is not found in humans. in the present study, the effects of α-bisabolol on aspergillus fumigatus af239 growth and ergosterol synthesis on the base of 24-smt enzyme activity were studied; in a ...201728224386
heterogeneity confounds establishment of "a" model microbial strain.aspergillus fumigatus is a ubiquitous environmental mold and the leading cause of diverse human diseases ranging from allergenic bronchopulmonary aspergillosis (abpa) to invasive pulmonary aspergillosis (ipa). experimental investigations of the biology and virulence of this opportunistic pathogen have historically used a few type strains; however, it is increasingly observed with this fungus that heterogeneity among isolates potentially confounds the use of these reference isolates. illustrating ...201728223452
in vitro and in vivo antifungal profile of a novel and long acting inhaled azole, pc945, on aspergillus fumigatus infection.the profile of pc945, a novel triazole antifungal, designed for administration via inhalation, has been assessed in a range of in vitro and in vivo studies. pc945 was characterized as a potent, tight-binding inhibitor of aspergillus fumigatus sterol 14α-demethylase (cyp51a and cyp51b) activity (ic50, 0.23 μm and 0.22 μm, respectively), with characteristic type ii azole binding spectra. against 96 clinically isolated a. fumigatus strains, the mic values of pc945 ranged from 0.032∼>8 μg/ml, whilst ...201728223388
bactericidal and fungicidal activity of n-chlorotaurine is enhanced in cystic fibrosis sputum medium.lung infections with multiresistant pathogens are a major problem of patients suffering from cystic fibrosis (cf). n-chlorotaurine (nct), a microbicidal active chlorine compound with no resistance development, is well tolerated upon inhalation. the aim of this study was to investigate nct on its bactericidal and fungicidal activity in vitro in artificial sputum medium (asm) mimicking the composition of cystic fibrosis mucus.the medium was inoculated with bacteria (staphylococcus aureus including ...201728223376
iron acquisition in fungal pathogens of humans.the devastating infections that fungal pathogens cause in humans are underappreciated relative to viral, bacterial and parasitic diseases. in recent years, the contributions to virulence of reductive iron uptake, siderophore-mediated uptake and heme acquisition have been identified in the best studied and most life-threatening fungal pathogens: candida albicans, cryptococcus neoformans and aspergillus fumigatus. in particular, exciting new work illustrates the importance of iron acquisition from ...201728217776
transcription factor afmac1 controls copper import machinery in aspergillus fumigatus.copper (cu) is an essential metal for all living organisms, although it is toxic in excess. filamentous fungus must acquire copper from its environment for growth. despite its essentiality for growth, the mechanisms that maintain copper homeostasis are not fully understood in filamentous fungus. to gain insights into copper homeostasis, we investigated the roles of a copper transcription factor afmac1 in the life-threatening fungus aspergillus fumigatus, a homolog of the yeast mac1. we observed ...201728215034
epigenetic modifier induced enhancement of fumiquinazoline c production in aspergillus fumigatus (ga-l7): an endophytic fungus from grewia asiatica l.present study relates to the effect of valproic acid, an epigenetic modifier on the metabolic profile of aspergillus fumigatus (ga-l7), an endophytic fungus isolated from grewia asiatica l. seven secondary metabolites were isolated from a. fumigatus (ga-l7) which were identified as: pseurotin a, pseurotin d, pseurotin f2, fumagillin, tryprostatin c, gliotoxin and bis(methylthio)gliotoxin. addition of valproic acid in the growth medium resulted in the alteration of secondary metabolic profile wit ...201728213885
regulation of sterol biosynthesis in the human fungal pathogen aspergillus fumigatus: opportunities for therapeutic development.sterols are a major component of eukaryotic cell membranes. for human fungal infections caused by the filamentous fungus aspergillus fumigatus, antifungal drugs that target sterol biosynthesis and/or function remain the standard of care. yet, an understanding of a. fumigatus sterol biosynthesis regulatory mechanisms remains an under developed therapeutic target. the critical role of sterol biosynthesis regulation and its interactions with clinically relevant azole drugs is highlighted by the bas ...201728203225
sybr safe(tm) efficiently replaces ethidium bromide in aspergillus fumigatus gene disruption.invasive aspergillosis is a disease responsible for high mortality rates, caused mainly by aspergillus fumigatus. the available drugs are limited and this disease continues to occur at an unacceptable frequency. gene disruption is essential in the search for new drug targets. an efficient protocol for a. fumigatus gene disruption was described but it requires ethidium bromide, a genotoxic agent, for dna staining. therefore, the present study tested sybr safe(tm), a non-genotoxic dna stain, in a. ...201728198513
mitochondrial camkii inhibition in airway epithelium protects against allergic asthma.excessive ros promote allergic asthma, a condition characterized by airway inflammation, eosinophilic inflammation, and increased airway hyperreactivity (ahr). the mechanisms by which airway ros are increased and the relationship between increased airway ros and disease phenotypes are incompletely defined. mitochondria are an important source of cellular ros production, and our group discovered that ca(2+)/calmodulin-dependent protein kinase ii (camkii) is present in mitochondria and activated b ...201728194433
first isolation of the pan-azole-resistant aspergillus fumigatus cyp51a tr46/y121f/t289a mutant in a uk patient. 201728193463
maternal house dust mite exposure during pregnancy enhances severity of house dust mite-induced asthma in murine offspring.atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. however, it is unclear whether maternal exposure to common human allergens such as house dust mite (hdm), in the absence of additional adjuvants, influences offspring asthma develo ...201728192144
chemical characteristics, antimicrobial and cytotoxic activities of the essential oil of egyptian cinnamomum glanduliferum bark.the essential oil isolated from the bark of cinnamomum glanduliferum (wall) meissn that grown in egypt was screened for the first time. the chemical composition was analyzed by gc and gc/mass. the antimicrobial activity of the oil was assessed using agar-well diffusion method toward representatives for each of gram-positive bacteria, gram-negative bacteria, and fungi. the cytotoxic activity was checked using three human cancer cell lines. twenty seven compounds were identified, representing 99.0 ...201728190283
[prevalence of sensitization to inhalant allergens in the immunology department from hospital de especialidades pediátricas maría, honduras, 2016].allergic diseases are a public health problem; estimates indicate that between 30% and 40% of the world population is affected by some allergy. knowing the prevalence of allergen sensitization allows for adequate diagnoses and treatments to be offered. in honduras there are no studies available in pediatric patients.201728188710
role of n-linked glycosylation in the enzymatic properties of a thermophilic gh 10 xylanase from aspergillus fumigatus expressed in pichia pastoris.n-glycosylation is a posttranslational modification commonly occurred in fungi and plays roles in a variety of enzyme functions. in this study, a xylanase (af-xyna) of glycoside hydrolase (gh) family 10 from aspergillus fumigatus harboring three potential n-glycosylation sites (n87, n124 and n335) was heterologously produced in pichia pastoris. the n-glycosylated af-xyna (wt) exhibited favorable temperature and ph optima (75°c and ph 5.0) and good thermostability (maintaining stable at 60°c). to ...201728187141
fatal disseminated rasamsonia infection in cystic fibrosis post-lung transplantation.disseminated fungal infections are a known serious complication in individuals with cystic fibrosis (cf) following orthotopic lung transplantation. aspergillus fumigatus and scedosporium species are among the more common causes of invasive fungal infection in this population. however, it is also important for clinicians to be aware of other emerging fungal species which may require markedly different antifungal therapies.201728185887
terbinafine-loaded wound dressing for chronic superficial fungal infections.in spite of developing new drugs and modern formulations, the treatments of chronic fungal infections are still challenging. fibrous wound dressings are new suggestions for the treatment of chronic superficial infections. in the present study, we formulated an antifungal agent, terbinafine hydrochloride (tfh), which is a hydrophobic drug, in wound dressings prepared by electrospun polycaprolactone, polycaprolactone/gelatin (50:50 w/w) and gelatin. to obtain more water-stable meshes, the preparat ...201728183589
structural, mechanistic and functional insight into gliotoxin bis-thiomethylation in aspergillus fumigatus.gliotoxin is an epipolythiodioxopiperazine (etp) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen aspergillus fumigatus self-resistance against gliotoxin is effected by the gliotoxin oxidase glit, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin s-methyltransferase gtma. here we describe the x-ray crystal structures of gtma-apo (1.66 å), gtma complexed to s-adenosylhomocysteine (1.33 ...201728179499
synthetic cystic fibrosis sputum medium diminishes <i>burkholderia cenocepacia</i> antifungal activity against <i>aspergillus fumigatus</i> independently of phenylacetic acid production.phenylacetic acid (paa), an intermediate of phenylalanine degradation, is emerging as a signal molecule in microbial interactions with the host. in this work, we explore the presence of phenylalanine and paa catabolism in three microbial pathogens of the cystic fibrosis (cf) lung microbiome: <i>pseudomonas aeruginosa</i>, <i>burkholderia cenocepacia</i> and <i>aspergillus fumigatus</i>. while <i>in silico</i> analysis of <i>b. cenocepacia</i> j2315 and <i>a. fumigatus</i> af293 genome sequences ...201728178425
prospective multicenter german study on pulmonary colonization with scedosporium /lomentospora species in cystic fibrosis: epidemiology and new association factors.an increasing rate of respiratory colonization and infection in cystic fibrosis (cf) is caused by fungi of the scedosporium apiospermum species complex or lomentospora prolificans (sac-lp). these fungi rank second among the filamentous fungi colonizing the cf airways, after aspergillus fumigatus. however, the epidemiology, clinical relevance and risk of pulmonary colonization with sac-lp are rarely understood in cf. the objective of the present prospective multicenter study was to study pathogen ...201728178337
[pulmonary co-infection due to nocardia cyriacigeorgica and aspergillus fumigatus].pulmonary nocardiosis is an uncommon pulmonary infection caused by aerobic gram-positive bacteria of the genus nocardia. nocardia sp. are environmental organisms spread worldwide. approximately 50 nocardia species have been described to date, about 30 of which are known to cause human disease. nocardia cyriacigeorgica was first reported in 2001.201728176520
a novel phosphoregulatory switch controls the activity and function of the major catalytic subunit of protein kinase a in aspergillus fumigatus.invasive aspergillosis (ia), caused by the filamentous fungal pathogen aspergillus fumigatus, is a major cause of death among immunocompromised patients. the cyclic amp/protein kinase a (pka) signaling pathway is essential for hyphal growth and virulence of a. fumigatus, but the mechanism of regulation of pka remains largely unknown. here, we discovered a novel mechanism for the regulation of pka activity in a. fumigatus via phosphorylation of key residues within the major catalytic subunit, pka ...201728174315
global population genetic analysis of aspergillus fumigatus.aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen capable of causing invasive aspergillosis, a globally distributed disease with a mortality rate of up to 90% in high-risk populations. effective control and prevention of this disease require a thorough understanding of its epidemiology. however, despite significant efforts, the global molecular epidemiology of a. fumigatus remains poorly understood. in this study, we analyzed 2,026 a. fumigatus isolates from 13 countries in fou ...201728168221
structure of the sliding clamp from the fungal pathogen aspergillus fumigatus (afumpcna) and interactions with human p21.the fungal pathogen aspergillus fumigatus has been implicated in a drastic increase in life-threatening infections over the past decade. however, compared to other microbial pathogens, little is known about the essential molecular processes of this organism. one such fundamental process is dna replication. the protein responsible for ensuring processive dna replication is pcna (proliferating cell nuclear antigen, also known as the sliding clamp), which clamps the replicative polymerase to dna. h ...201728165677
ram1 gene, encoding a subunit of farnesyltransferase, contributes to growth, antifungal susceptibility to amphotericin b of aspergillus fumigatus. 201728159997
broad spectrum anti-infective properties of benzisothiazolones and the parallels in their anti-bacterial and anti-fungal effects.various mono- and bis-benzisothiazolone derivatives were synthesized and screened against different strains of bacteria and fungi in order to understand the effect of multiple electrophilic sulfur atoms and substitution pattern in the immediate vicinity of reactive sulfur. staphyllococcus aureus-atcc 7000699, mrsa and s. aureus-atcc 29213 (quality control strain) were more susceptible to this class of compounds, and the most potent derivative 1.15 had mic50 of 0.4μg/ml (cf. gentamicin=0.78μg/ml) ...201728159413
the role of mincle in innate immune to fungal keratitis.this study aimed to detect the early expression of macrophage-inducible c-type lectin (mincle) and investigate its role in the innate immune response of fungal keratitis (fk).201728141595
household proximity to water and nontuberculous mycobacteria in children with cystic fibrosis.nontuberculous mycobacteria (ntm) have a particular affinity for patients with cystic fibrosis (cf). recent studies suggest a possible relationship between acquiring ntm and the level of environmental water in a given area. we sought to determine if there is an association between household proximity to water and ntm in children with cf.201728135043
conserved cysteine residues determine substrate specificity in a novel as(iii) s-adenosylmethionine methyltransferase from aspergillus fumigatus.methylation of inorganic arsenic is a central process in the organoarsenical biogeochemical cycle. members of every kingdom have arsm as(iii) s-adenosylmethionine (sam) methyltransferases that methylates inorganic as(iii) into mono- (mas(iii)), di- (dmas(iii)) and tri- (tmas(iii)) methylarsenicals. every characterized arsm to date has four conserved cysteine residues. all four cysteines are required for methylation of as(iii) to mas(iii), but methylation of mas(iii) to dmas(iii) requires only th ...201728127843
differential roles of caspase-1 and caspase-11 in infection and inflammation.caspase-1, also known as interleukin-1β (il-1β)-converting enzyme (ice), regulates antimicrobial host defense, tissue repair, tumorigenesis, metabolism and membrane biogenesis. on activation within an inflammasome complex, caspase-1 induces pyroptosis and converts pro-il-1β and pro-il-18 into their biologically active forms. "ice(-/-)" or "casp1(-/-)" mice generated using 129 embryonic stem cells carry a 129-associated inactivating passenger mutation on the caspase-11 locus, essentially making t ...201728345580
funresdb-a web resource for genotypic susceptibility testing of aspergillus fumigatus.therapy of invasive aspergillosis is becoming more difficult due to the emergence of azole resistance in aspergillus fumigatus. a majority of resistant strains carries mutations in the cyp51a gene. due to a lack of sensitivity of culture-based methods, molecular detection of a. fumigatus has become an important diagnostic tool. we set up the database funresdb (www.nrz-myk.de/funresdb) to gather all available information about cyp51a-dependent azole resistance from published literature. in summar ...201728340175
detection of polish clinical aspergillus fumigatus isolates resistant to triazoles.we studied the presence of triazole resistance of 121 aspergillus fumigatus clinical isolates collected in two polish cities, warsaw and wrocław, to determine if resistance is emerging in our country. we identified five itraconazole resistant isolates (4.13%) carrying the tr34/l98h alteration in cyp51a gene, four of which were cross-resistant to posaconazole and one to voriconazole. one isolate was intermediate susceptible to itraconazole and harbored no cyp51a alterations. the study confirms th ...201728340159
dirhamnolipids secreted from pseudomonas aeruginosa modify anjpegungal susceptibility of aspergillus fumigatus by inhibiting β1,3 glucan synthase activity.pseudomonas aeruginosa and aspergillus fumigatus are the two microorganisms responsible for most of the chronic infections in cystic fibrosis patients. p. aeruginosa is known to produce quorum-sensing controlled rhamnolipids during chronic infections. here we show that the dirhamnolipids secreted from p. aeruginosa (i) induce a. fumigatus to produce an extracellular matrix, rich in galactosaminogalactan, 1,8-dihydroxynaphthalene (dhn)- and pyo-melanin, surrounding their hyphae, which facilitates ...201728338676
synthesis and biological evaluation of a new series of benzimidazole derivatives as antimicrobial, antiquorum-sensing and antitumor agents.new benzimidazole derivatives were synthesized and assessed for antimicrobial efficacy toward escherichia coli, bacillus cereus, staphylococcus aureus, candida albicans and aspergillus fumigatus 293. results indicated that compounds 3c and 3n have promising activity toward s. aureus, whereas 3i exhibited remarkable efficacy toward b. cereus. moreover, compound 3c was proved to be the most active antifungal analog toward c. albicans. on the other hand, 3n displayed the highest activity against a. ...201728334654
evaluation of a real-time impedance analysis platform on fungal infection.end-point assays of in vitro cell proliferation and death have been employed to study the mechanisms of fungal pathogenesis and have shown the responses of host cells at individual time points. a new cell analysis technology has been developed that allows for the continuous measurement and quantification of cell activities, thus enabling the dynamic assessment of electrical impedance when various pathogens are cultured in vitro. in this study, this system was evaluated to determine the response ...201728323067
synthesis, characterization and antimicrobial activity of biguanidinylated chitosan-g-poly[(r)-3-hydroxybutyrate].chitosan biguanidine hydrochloride (chg) and low molecular weight poly[(r)-3-hydroxybutyrate] (phb) were successfully prepared to overcome the solubility problem of chitosan and phb and also to enhance antimicrobial activity of chitosan. the graft copolymers based on chg and phb (chg-grafted phb) were then prepared via condensation reaction of the carboxylic groups of phb with the amino groups of chg. these graft copolymers swell in water. the prepared graft copolymers were characterized by ftir ...201728322958
characterization of a pa14 domain-containing galactofuranose-specific β-d-galactofuranosidase from streptomyces sp.as a constituent of polysaccharides and glycoconjugates, β-d-galactofuranose (galf) exists in several pathogenic microorganisms. although we recently identified a β-d-galactofuranosidase (galf-ase) gene, orf1110, in the streptomyces strain jha19, very little is known about the galf-ase gene. here, we characterized a strain, named jha26, in the culture supernatant of which exhibited galf-ase activity for 4-nitrophenyl β-d-galactofuranoside (pnp-β-d-galf) as a substrate. draft genome sequencing of ...201728317475
aspergillus pericarditis with tamponade in a renal transplant patient.aspergillus pericarditis is a rare and life-threatening infection in immunosuppressed patients. it has nonspecific clinical manifestations that often mimic other disease entities especially in patients who have extensive comorbidities. diagnosis is oftentimes delayed and rarely done antemortem. a high degree of suspicion in immunocompromised patients is necessary for evaluation and timely diagnosis. this is a case of aspergillus pericarditis with cardiac tamponade in a renal transplant patient w ...201728316844
triazole resistance in aspergillus fumigatus clinical isolates obtained in nanjing, china.during the past decades, the incidence of invasive aspergillosis (ia) caused by aspergillus fumigatus has increased dramatically. the aims of this study were to investigate the susceptibility of clinical isolates of a. fumigatus to triazole and the underlying cyp51a mutations in triazole-resistant a. fumigatus.201728303848
aspergillosis, a natural infection in poultry: mycological and molecular characterization and determination of gliotoxin in aspergillus fumigatus isolates.aspergillosis affects all types of birds; it causes the loss of specimens with high ecologic value and also leads to significant economic losses within the poultry industry. the main etiologic agent is aspergillus fumigatus , a filamentary fungus with multiple virulence factors, such as gliotoxin (gt), which is an immunosuppressive epipolythiodioxopiperazine molecule. necropsy was performed on 73 poultry from different provenances, all of which presented with a respiratory semiology compatible w ...201728301237
challenges in microbiological diagnosis of invasive aspergillus infections.invasive aspergillosis (ia) has been increasingly reported in populations other than the historical hematology patients and there are new questions about the performance of microbiological tools. microscopy and culture have been completed by biomarkers, either antigens or dna, and in blood or respiratory specimens or both. first studied in hematology, the antigen galactomannan performance in serum is low in other patient populations where the pathophysiology of the infection can be different and ...201728299183
central role of the trehalose biosynthesis pathway in the pathogenesis of human fungal infections: opportunities and challenges for therapeutic development.invasive fungal infections cause significant morbidity and mortality in part due to a limited antifungal drug arsenal. one therapeutic challenge faced by clinicians is the significant host toxicity associated with antifungal drugs. another challenge is the fungistatic mechanism of action of some drugs. consequently, the identification of fungus-specific drug targets essential for fitness in vivo remains a significant goal of medical mycology research. the trehalose biosynthetic pathway is found ...201728298477
[the regulative effects of aspergillus fumigatus on expression of glucocorticoid receptor in asthmatic rats].objective: to study the regulative effects of aspergillus fumigatus (a.fumigatus) on expression of glucocorticoid receptor (gcr) in asthmatic rats. methods: wistar rats were randomly divided into 4 groups: a normal control group (uc), a normal control with a. fumigatus group (uc+ af), an ova group (ova), and an ova with a. fumigatus group (ova+ af). ova and ova+ af groups were sensitized and challenged with ova to establish asthmatic models. uc and uc+ af groups were given normal saline as contr ...201728297812
epidemiology of multidrug-resistant gram-negative pathogens isolated from ventilator-associated pneumonia in icu patients.antibiotic resistance among gram-negative pathogens isolated from ventilator-associated pneumonia (vap) poses a grave threat in intensive care unit (icu) patients. the aim of this study was to assess the prevalence of pathogens in icu patients and their drug resistance profile. the prevalence of extended-spectrum β-lactamases (esbls), ampc β-lactamases and metallo-β-lactamases (mbls) was also assessed.201728288860
two new sesquiterpene lactone glycosides from cnicus benedictus.two new sesquiterpene lactone glycosides, namely melitensin 15-o-β-d-glucoside (1) and 11β,13-dihydrosalonitenolide 15-o-β-d-glucoside (2), along with eight known compounds (3-10) were isolated from the aerial part of cnicus benedictus l. their structures were elucidated from analyses of extensive spectroscopic data. compounds 1-6 all possessed an α-methyl-γ-lactone moiety. moreover, compound 5 exhibited moderate activity against the growth of aspergillus fumigatus, with ic50 values of 17.67 μg  ...201728287272
lah is a transmembrane protein and requires spa10 for stable positioning of woronin bodies at the septal pore of aspergillus fumigatus.woronin bodies are specialized, fungal-specific organelles that enable an immediate closure of septal pores after injury to protect hyphae from excessive cytoplasmic bleeding. in most ascomycetes, woronin bodies are tethered at the septal pore by so-called lah proteins. using the pathogenic mold aspergillus fumigatus as a model organism, we show that the c-terminal 288 amino acids of lah (lahc288) bind to the rim of the septal pore. lahc288 essentially consists of a membrane spanning region and ...201728281662
specific and novel micrornas are regulated as response to fungal infection in human dendritic cells.within the last two decades, the incidence of invasive fungal infections has been significantly increased. they are characterized by high mortality rates and are often caused by candida albicans and aspergillus fumigatus. the increasing number of infections underlines the necessity for additional anti-fungal therapies, which require extended knowledge of gene regulations during fungal infection. micrornas are regulators of important cellular processes, including the immune response. by analyzing ...201728280489
contributions of both atp-binding cassette transporter and cyp51a proteins are essential for azole resistance in aspergillus fumigatus.while azole drugs targeting the biosynthesis of ergosterol are effective antifungal agents, their extensive use has led to the development of resistant organisms. infections involving azole resistant forms of the filamentous fungus aspergillus fumigatus are often associated with genetic changes in the cyp51a gene encoding the lanosterol α14 demethylase target enzyme. both a sequence duplication in the cyp51a promoter (tr34) as well as a substitution mutation in the coding sequence (l98h) are req ...201728264842
diversity, phylogeny, anticancer and antimicrobial potential of fungal endophytes associated with monarda citriodora l.present study focuses on diversity and distribution analysis of endophytic fungi associated with different tissues of the monarda citriodora cerv. ex lag. (lamiaceae/labiatae). anticancer and antimicrobial potential of isolated endophytes have also been investigated.201728264654
post-influenza aspergillosis, do not underestimate influenza b.our objective is to highlight and focus on post-influenza aspergillosis, triggered by influenza b virus. this relatively new clinical entity is often associated with a fulminant course of respiratory decline and high mortality. a 51-year immunocompetent woman, without any medical history or risk factors for developing a complicated influenza infection, was admitted to the intensive care unit. during admission, she presented with an afebrile flu-like syndrome, myocarditis, rhabdomyolysis, multipl ...201728260935
culture-positive pulmonary aspergillosis infection: clinical and laboratory features of solid-organ transplant recipients.aspergillosis is a common fungal infection among solid-organ transplant recipients. even after awareness of this infection occurs, there are still gaps in nonculture diagnostic tests, which can delay treatment initiation. here, we aimed to define the common traits of pulmonary aspergillosis infection among solid-organ transplant recipients, thus shedding light on prevention and early diagnosis.201728260471
insights into the unprecedented epoxidation mechanism of fumitremorgin b endoperoxidase (ftmox1) from aspergillus fumigatus by qm/mm calculations.fumitremorgin b endoperoxidase (ftmox1) from aspergillus fumigatus is the first reported α-ketoglutarate-dependent mononuclear non-haem iron enzyme that catalyzes the endoperoxide formation reaction, converting fumitremorgin b to verruculogen. experiments reveal that the molecular oxygen (o2) is incorporated into verruculogen without o-o bond scission, which differs from the currently known non-haem iron enzymes, but the mechanistic details are still unclear. in this paper, on the basis of the c ...201728256663
resistance of aspergillus fumigatus to micafungin is increased by exogenous β-glucan.aspergillus species are ubiquitous in the environment and aspergillus fumigatus can cause life-threatening infections in immunocompromised patients. β-1,3-/1,6-glucan is a major fungal cell wall polysaccharide that has various biological effects on the infected host, but little is known about the influence of β-glucan on the fungus itself. in a previous study, we demonstrated that the cell wall β-glucan content could be increased in aspergillus spp. by addition of β-glucan to the culture medium. ...201728250363
infections in severe alcoholic hepatitis.severe alcoholic hepatitis (sah), defined by a modified discriminant function ≥32, is the most severe form of alcohol-induced liver disease and is associated with a 1-month mortality rate of around 30%. corticosteroid treatment remains the only therapeutic option that improves short-term survival. infectious complications, occurring in approximately 50% of patients, are the main causes of death, even in patients who benefit from corticosteroids. liver failure, recent alcohol consumption and immu ...201728243035
caspofungin exposure alters the core septin aspb interactome of aspergillus fumigatus.aspergillus fumigatus, the main etiological agent of invasive aspergillosis, is a leading cause of death in immunocompromised patients. septins, a conserved family of gtp-binding proteins, serve as scaffolding proteins to recruit enzymes and key regulators to different cellular compartments. deletion of the a. fumigatus septin aspb increases susceptibility to the echinocandin antifungal caspofungin. however, how aspb mediates this response to caspofungin is unknown. here, we characterized the as ...201728238781
aryl-alkyl-lysines: membrane-active fungicides that act against biofilms of candida albicans.mortality due to pathogenic fungi has been exacerbated by the rapid development of resistance to frontline antifungal drugs. fungicidal compounds with novel mechanisms of action are urgently needed. aryl-alkyl-lysines, which are membrane-active small molecules, were earlier shown to be broad-spectrum antibacterial agents with potency in vitro and in vivo. herein, we report the antifungal properties of aryl-alkyl-lysines. after identifying the most active compound (nck-10), we tested its activity ...201728238268
triazole resistance in aspergillus species: an emerging problem.aspergillus species are ubiquitous fungal saprophytes found in diverse ecological niches worldwide. among them, aspergillus fumigatus is the most prevalent and is largely responsible for the increased incidence of invasive aspergillosis with high mortality rates in some immunocompromised hosts. azoles are the first-line drugs in treating diseases caused by aspergillus spp. however, increasing reports in a. fumigatus azole resistance, both in the clinical setting and in the environment, are threa ...201728236169
subacute invasive pulmonary aspergillosis as a rare cause of pneumothorax in immunocompetent patient: brief report.subacute invasive pulmonary aspergillosis (ipa) represents a form of chronic pulmonary aspergillosis which affects immunocompetent individuals or mildly immunocompromised persons with underlying pulmonary disease. pneumothorax can be a rare complication of subacute ipa due to a leakage of air from an air-filled lung cavitation into the pleural space. herein, we report rare and unusual case of pneumothorax in a patient with pulmonary cavity infection. a 40-year-old woman was admitted to thoracic ...201728233110
first clinical isolation report of azole-resistant aspergillus fumigatus with tr34/l98h-type mutation in japan.recently, azole-resistant aspergillus fumigatus containing a 34-bp or 46-bp tandem repeat in the promoter region of cyp51a combined with amino acid substitution(s) has appeared in the environment worldwide, including several asian countries. in this study, we isolated the 34-bp tandem repeat-containing azole-resistant a. fumigatus strain okh50 from a patient in japan in may 2016. the patient had not been treated with medical azoles before the strain isolation, suggesting that the resistant prope ...201728109740
renal allograft aspergillus infection presenting with obstructive uropathy: a case report.isolated renal allograft aspergillosis is rare and usually presents with fever and decreased glomerular filtration rate. presentation with obstructive uropathy caused by aspergillus fungal balls is much less common. we report a young male patient who presented with obstructive uropathy secondary to isolated renal allograft aspergillus infection 6 weeks after transplant. he was treated with nephrectomy and antifungal medications.201728104135
sputum inflammatory mediators are increased in aspergillus fumigatus culture-positive asthmatics.aspergillus fumigatus sensitization and culture in asthma are associated with disease severity and lung function impairment, but their relationship with airway inflammation is poorly understood. we investigated the profile of 24 sputum inflammatory mediators in a. fumigatus culture-positive or-negative moderate-to-severe asthmatics. fifty-two subjects were recruited from a single center. a. fumigatus was cultured from 19 asthmatics. asthma control, symptom score, lung function, and sputum cell c ...201728102063
etv5 regulates il-10 production in th cells.il-10 is an immunoregulatory cytokine that has broad effects across the immune system. in th cell subsets, th2 cells produce considerable amounts of il-10. the transcription factors that regulate il-10 production in th2 cells are still incompletely described. in this study, we demonstrate that the ets family transcription factor ets variant (etv)5 regulates il-10 production in th2 cells. t cell-specific etv5-deficient and littermate control mice demonstrated that il-10 production and gene expres ...201728100679
central role of il-23 and il-17 producing eosinophils as immunomodulatory effector cells in acute pulmonary aspergillosis and allergic asthma.aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. we studied the contribution of lung eosinophils to these fungal diseases. by in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of il-23 and il-17. remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung il-23p19+ cells as well as markedly reduced il-23 heterodimer in lung lavage f ...201728095479
differential effects of vitamins a and d on the transcriptional landscape of human monocytes during infection.vitamin a and vitamin d are essential nutrients with a wide range of pleiotropic effects in humans. beyond their well-documented roles in cellular differentiation, embryogenesis, tissue maintenance and bone/calcium homeostasis, both vitamins have attracted considerable attention due to their association with-immunological traits. nevertheless, our knowledge of their immunomodulatory potential during infection is restricted to single gene-centric studies, which do not reflect the complexity of im ...201728094291
first itraconazole resistant aspergillus fumigatus clinical isolate harbouring a g54e substitution in cyp51ap in south america.a 27-year-old male rural worker was admitted with a fungal keratitis due to an injury involving plant detritus.201728087293
cipc is important for aspergillus fumigatus virulence.aspergillus fumigatus is the main causative agent of invasive aspergillosis, a disease that affects immunocompromised patients and has a high mortality rate. we previously observed that the transcription of a cipc-like gene was increased when a. fumigatus encountered an increased co2 concentration, as occurs during the infection process. cipc is a protein of unknown function that might be associated with fungal pathogenicity. in this study, the cipc gene was disrupted in a. fumigatus to evaluate ...201728120495
synergistic effects of tetrandrine with posaconazole against aspergillus fumigatus.in our earlier in vitro and in vivo studies, synergistic effects were observed when itraconazole or voriconazole were combined with tetrandrine (tet) against aspergillus fumigatus, and the synergistic mechanism was related to inhibition of the drug efflux pump. posaconazole (pcz) is a broad-spectrum triazole antifungal agent used for the treatment of diverse fungal infections, including aspergillosis and candidiasis. herein, the antifungal effects of tet are further investigated in vitro and in ...201728080217
neutrophil interactions stimulate evasive hyphal branching by aspergillus fumigatus.invasive aspergillosis (ia), primarily caused by aspergillus fumigatus, is an opportunistic fungal infection predominantly affecting immunocompromised and neutropenic patients that is difficult to treat and results in high mortality. investigations of neutrophil-hypha interaction in vitro and in animal models of ia are limited by lack of temporal and spatial control over interactions. this study presents a new approach for studying neutrophil-hypha interaction at single cell resolution over time ...201728076396
activity of a long-acting echinocandin (cd101) and seven comparator antifungal agents tested against a global collection of contemporary invasive fungal isolates in the sentry 2014 antifungal surveillance program.the activity of cd101 and comparator antifungal agents against 606 invasive fungal isolates collected worldwide during 2014 was evaluated using the clinical and laboratory standards institute (clsi) method. all candida albicans (n = 251), candida tropicalis (n = 51), candida krusei (n = 16), and candida dubliniensis (n = 11) isolates were inhibited by ≤0.12 μg/ml of cd101 and were susceptible or showed wild-type susceptibility to the other echinocandins tested. five c. glabrata isolates (n = 100 ...201728052853
modelling the effect of ph and water activity in the growth of aspergillus fumigatus isolated from corn silage.the aim of this work was to use mathematical kinetic modelling to assess the combined effects of aw, ph, o2 availability and temperature on the growth rate and time to growth of aspergillus fumigatus strains isolated from corn silage.201728052586
a novel zn2-cys6 transcription factor atrr plays a key role in an azole resistance mechanism of aspergillus fumigatus by co-regulating cyp51a and cdr1b expressions.successful treatment of aspergillosis caused by aspergillus fumigatus is threatened by an increasing incidence of drug resistance. this situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. to elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in aspergillus fungi including a. fumigatus, as ...201728052140
damage resistance protein (dap) contributes to azole resistance in a sterol-regulatory-element-binding protein srba-dependent way.the targeting of stress-response regulators has emerged as a powerful strategy to enhance azole drug efficacy and to abrogate azole drug resistance. previously, we reported that a damage resistance protein (dap) family, composed of dapa, dapb, and dapc, could respond to azole stress stimuli in aspergillus fumigatus, although the exact response mechanisms remain unknown. in this study, rna-seq analysis found that a total of 180 genes are induced by azole in a dapa-dependent manner. these genes ar ...201728050634
structure of a fungal form of aspartate-semialdehyde dehydrogenase from aspergillus fumigatus.aspartate-semialdehyde dehydrogenase (asadh) functions at a critical junction in the aspartate biosynthetic pathway and represents a validated target for antimicrobial drug design. this enzyme catalyzes the nadph-dependent reductive dephosphorylation of β-aspartyl phosphate to produce the key intermediate aspartate semialdehyde. the absence of this entire pathway in humans and other mammals will allow the selective targeting of pathogenic microorganisms for antimicrobial development. here, the x ...201728045392
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