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interactions between copy number and expression level of genes involved in fluconazole resistance in candida glabrata.this study aimed to elucidate the relative involvement of drug resistance gene copy number and overexpression in fluconazole resistance in clinical c. glabrata isolates using a population-based approach.201324273749
biological activities of commercial bee pollens: antimicrobial, antimutagenic, antioxidant and anti-inflammatory.bee pollen is considered, since memorable times, a good source of nourishing substances and energy. the present study aimed to evaluate the biological activities of eight commercial bee pollens purchased from the market. the origin of sample a was not specified in the labeling; samples b, c, d and g were from portugal and the remaining were from spain. the sample e presented the highest value of phenolics (32.15±2.12 mg/g) and the h the lowest (18.55±095 mg/g). sample c had the highest value of ...201424262487
the mating type-like loci of candida glabrata.candida glabrata, a haploid and opportunistic fungal pathogen that has not known sexual cycle, has conserved the majority of the genes required for mating and cell type identity. the c. glabrata genome contains three mating-type-like loci called mtl1, mtl2 and mtl3. the three loci encode putative transcription factors, a1, α1 and α2 that regulate cell type identity and sexual reproduction in other fungi like the closely related saccharomyces cerevisiae. mtl1 can contain either a or α information ...201424252826
candida glabrata: a review of its features and resistance.candida species belong to the normal microbiota of the oral cavity and gastrointestinal and vaginal tracts, and are responsible for several clinical manifestations, from mucocutaneous overgrowth to bloodstream infections. once believed to be non-pathogenic, candida glabrata was rapidly blamable for many human diseases. year after year, these pathological circumstances are more recurrent and problematic to treat, especially when patients reveal any level of immunosuppression. these difficulties a ...201424249283
chemical composition and antimicrobial activity of the essential oil from the edible aromatic plant aristolochia delavayi.the essential oil obtained by hydrodistillation from the aerial parts of aristolochia delavayi franch. (aristolochiaceae), a unique edible aromatic plant consumed by the nakhi (naxi) people in yunnan, china, was investigated using gc/ms analysis. in total, 95 components, representing more than 95% of the oil composition, were identified, and the main constituents found were (e)-dec-2-enal (52.0%), (e)-dodec-2-enal (6.8%), dodecanal (3.35%), heptanal (2.88%), and decanal (2.63%). the essential oi ...201324243612
prevalence and risk factors of onychomycosis in primary school children living in rural and urban areas in central anatolia of turkey.onychomycosis is a world-wide public health concern in children, requiring epidemiological data for different regions for control and prevention.201324177609
a patient with interstitial lung disease secondary to dermatomyositis: a case report and review of the literature.we describe the case of a man with known dermatomyositis who presented with a dry cough and who early after admission rapidly evolved to respiratory insufficiency. based on pathological and radiological findings, the diagnosis of diffuse alveolar damage was made. postmortem examination also revealed infection with yeast, torulopsis glabrata. polymyositis (pm) and dermatomyositis (dm) are both auto-immune diseases, which are characterised by the presence of auto-antibodies and tissue-inflammation ...201624156232
frequency of fks mutations among candida glabrata isolates from a 10-year global collection of bloodstream infection isolates.among 119 echinocandin non-wild-type (non-wt) candida glabrata strains from two global surveys, mutations in fks hot spots (hss) were detected in 28 (from 7 countries and 8 u.s. states): 24 strains (85.7%) had non-wt mics for micafungin, 22 (78.6%) for anidulafungin, and 25 (89.3%) for caspofungin. the most common fks substitutions among non-wt strains were at positions f659 (n = 7) and s663 (n = 7). three isolates displaying wt mic results had f625y, l630i, and d632y substitutions or non-hs mut ...201424126582
urea enhances cell growth and pyruvate production in torulopsis glabrata.torulopsis glabrata is a strain of yeast that is used for the industrial production of pyruvate. determination of the optimal nutrient environment is vital for obtaining the most efficient production system. in this study, the fermentation parameters, gene transcription levels, activities of key enzymes and metabolites levels were analyzed when either urea or ammonium chloride was used as the sole source of nitrogen. urea caused an increase in the dry cell weight (18%) and pyruvate productivity ...201424124177
antifungal resistance does not necessarily affect candida glabrata fitness.although there has been an overall good coverage of candida glabrata infections by the echinocandins, emergence of antifungal resistance during therapy has been reported. we investigated, by using an invertebrate host model, the fitness of sequential c. glabrata isolates with different echinocandins susceptibility patterns. the studied strains were isolated from a case of recurrent fungemia with a fatal outcome due to c. glabrata that developed cross-resistance to echinocandins during caspofungi ...201424091025
anidulafungin and micafungin mic breakpoints are superior to that of caspofungin for identifying fks mutant candida glabrata strains and echinocandin resistance.by clsi interpretive criteria, anidulafungin and micafungin mics determined by various methods were sensitive (60 to 70%) and highly specific (94 to 100%) for identifying fks mutations among 120 candida glabrata isolates. anidulafungin and micafungin breakpoints were more specific than clsi's caspofungin breakpoint in identifying fks mutant strains and patients with invasive candidiasis who were likely to fail echinocandin treatment (p ≤ 0.0001 for both). echinocandin mics were most useful clini ...201324060873
elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase.the pursuit of antimicrobial drugs that target dihydrofolate reductase (dhfr) exploits differences in sequence and dynamics between the pathogenic and human enzymes. here, we present five crystal structures of human dhfr bound to a new class of antimicrobial agents, the propargyl-linked antifolates (plas), with a range of potency (ic50 values of 0.045-1.07 μm) for human dhfr. these structures reveal that interactions between the ligands and asn 64, phe 31, and phe 34 are important for increased ...201324053334
treatment of invasive candidiasis in the elderly: a review.fungi are major causes of infections among immunocompromised or hospitalized patients with serious underlying diseases and comorbidities. candida species remain the most important cause of opportunistic infections worldwide, affecting predominantly patients over 65 years old, while they are considered to be the fourth most common cause of nosocomial bloodstream infections. the rapidly growing elderly population has specific physiological characteristics, which makes it susceptible to colonizatio ...201324043935
comparative genomics of emerging pathogens in the candida glabrata clade.candida glabrata follows c. albicans as the second or third most prevalent cause of candidemia worldwide. these two pathogenic yeasts are distantly related, c. glabrata being part of the nakaseomyces, a group more closely related to saccharomyces cerevisiae. although c. glabrata was thought to be the only pathogenic nakaseomyces, two new pathogens have recently been described within this group: c. nivariensis and c. bracarensis. to gain insight into the genomic changes underlying the emergence o ...201324034898
candidaemia in the non-neutropenic patient: a critique of the guidelines.several guidelines have been published on the management of candidaemia. these guidelines vary in their recommendations, and the lack of consistency between the guidelines has implications for the management of candidaemia. we critiqued five guidelines, including the infectious diseases society of america (idsa) guidelines for the management of candidiasis, the canadian clinical practice guidelines for invasive candidiasis in adults, the joint recommendations of the german speaking mycological s ...201324016797
pediatric risk factors for candidemia secondary to candida glabrata and candida krusei species.this 13-year retrospective study investigated risk factors for candidemia secondary to candida species with increased likelihood of fluconazole resistance. of 344 candidemia cases, 23 were caused by c glabrata or c krusei (cgck). age >2 years, recent fluconazole exposure, and recent surgery were independent risk factors for cgck.201324009984
flucytosine antagonism of azole activity versus candida glabrata: role of transcription factor pdr1 and multidrug transporter cdr1.infections with the opportunistic yeast candida glabrata have increased dramatically in recent years. antifungal therapy of yeast infections commonly employs azoles, such as fluconazole (flc), but c. glabrata frequently develops resistance to these inhibitors of ergosterol biosynthesis. the pyrimidine analog flucytosine (5-fluorocytosine [5fc]) is highly active versus c. glabrata but is now rarely used clinically due to similar concerns over resistance and, a related concern, the toxicity associ ...201323979762
cutaneous candidiasis caused by candida glabrata in a hiv/aids patient.cutaneous candida infections may occur in patients with hiv/aids, cancer, receiving chemotherapy and solid organ transplantation. a 32-year-old woman was admitted to the department suffering from pruritic and erythematous plaque on left side of her face for the past two months. the patient was hiv positive, diagnosed five years previously, and had been on antiretroviral therapy (tenofovir/emtricitabine and lopinavir/ritonavir) for a year. she was not compliant with the medication. elevated hiv r ...201323970580
breakthrough invasive fungal diseases during echinocandin treatment in high-risk hospitalized hematologic patients.the frequency of breakthrough invasive fungal diseases (ifds) during echinocandin therapy is unclear. we retrospectively analyzed 534 hematologic patients treated with echinocandin (caspofungin, n = 55; micafungin, n = 306; anidulafungin, n = 173). four proven ifds were found, caused by candida parapsilosis (n = 2), c. parapsilosis and candida glabrata (n = 1), and fusarium species (n = 1). four cases of possible ifds were observed, all showing pulmonary infection. one case showed features sugge ...201423949318
mutation of the cgpdr16 gene attenuates azole tolerance and biofilm production in pathogenic candida glabrata.the pdr16 gene encodes the homologue of sec14p, participating in protein secretion, regulation of lipid synthesis and turnover in vivo and acting as a phosphatidylinositol transfer protein in vitro. this gene is also involved in the regulation of multidrug resistance in saccharomyces cerevisiae and pathogenic yeasts. here we report the results of functional analysis of the cgpdr16 gene, whose mutation has been previously shown to enhance fluconazole sensitivity in candida glabrata mutant cells. ...201323939632
a mouse model for candida glabrata hematogenous disseminated infection starting from the gut: evaluation of strains with different adhesion properties.adhesion to digestive mucosa is considered a crucial first step in the pathogenicity of invasive candida infections. candida glabrata disseminated infections predominantly start from the gut. a mouse model of disseminated infection starting from the gut was set up. hematogenous dissemination was obtained after a low-protein diet followed by a regimen of cyclophosphamide-methotrexate and an oral inoculation of the yeasts via the drinking water. the liver was the first organ infected (day 7 post-i ...201323936069
expression plasmids for use in candida glabrata.we describe a series of cen/ars episomal plasmids containing different candida glabrata promoters, allowing for a range of constitutive or regulated expression of proteins in c. glabrata. the set of promoters includes three constitutive promoters (egd2pr, hht2pr, pdc1pr), two macrophage/phagocytosis-induced promoters (aco2pr, lys21pr), and one nutritionally regulated promoter (met3pr). each promoter was cloned into two plasmid backbones that differ in their selectable marker, ura3, or the domina ...201323934995
catalysis product captured in lumazine synthase from the fungal pathogen candida glabrata.candida glabrata has emerged as an important fungal pathogen with intrinsic resistance to azole drugs. the limited efficacy of and resistance to existing antifungals is driving the need to identify new drug targets. the enzyme 6,7-dimethyl-8-(d-ribityl)lumazine synthase is part of the riboflavin-biosynthesis pathway essential to fungi and bacteria and is a potential drug target for the development of broad-spectrum antifungal drugs. the x-ray crystal structure of recombinant lumazine synthase fr ...201323897480
the fate of linear dna in saccharomyces cerevisiae and candida glabrata: the role of homologous and non-homologous end joining.in vivo assembly of plasmids has become an increasingly used process, as high throughput studies in molecular biology seek to examine gene function. in this study, we investigated the plasmid construction technique called gap repair cloning (grc) in two closely related species of yeast - saccharomyces cerevisiae and candida glabrata. grc utilizes homologous recombination (hr) activity to join a linear vector and a linear piece of dna that contains base pair homology. we demonstrate that a minimu ...201323894512
deficiencies in mitochondrial dna compromise the survival of yeast cells at critically high temperatures.to address possible roles of mitochondrial genes in adaptation of eukaryotic cells to critical temperatures, we compared thermotolerance of mitochondrial rho mutants and wild type cells of six rho positive yeast species: candida glabrata, saccharomyces bayanus, saccharomyces cerevisiae, saccharomyces eubayanus, saccharomyces paradoxus and saccharomyces pastorianus. all rho mutants manifested compromised thermotolerance as a common phenotype. analysis of viabilities at critical temperatures (32-4 ...201423890722
pyruvate production in candida glabrata: manipulation and optimization of physiological function.candida glabrata, a multi-vitamin auxotrophic yeast, can accumulate a large amount of pyruvate extracellularly using glucose as the carbon source, a characteristic that has facilitated the cost-effective biotechnological production of pyruvate on an industrial scale. in this review, we describe the current advances in further improving the performance of c. glabrata for efficient pyruvate production, which includes: optimization of the vitamin and dissolved oxygen concentrations, regulation of i ...201623883073
rapid and reliable maldi-tof mass spectrometry identification of candida non-albicans isolates from bloodstream infections.matrix-assisted laser desorption/ionization time-of-flight (maldi-tof) mass spectrometry (ms) fingerprinting has recently become an effective instrument for rapid microbiological diagnostics and in particular for identification of micro-organisms directly in a positive blood culture. the aim of the study was to evaluate a collection of 82 stored yeast isolates from bloodstream infection, by maldi-tof ms; 21 isolates were identified also directly from positive blood cultures and in the presence o ...201323845229
usefulness of time-to-positivity in aerobic and anaerobic vials to predict the presence of candida glabrata in patients with candidaemia.to determine whether time-to-positivity (ttp) in aerobic and anaerobic blood culture vials is useful to predict the presence of candida glabrata in patients with candidaemia.201323843300
caspofungin benefit on phagocytes from patients with renal dysfunction infected with multidrug-resistant candida glabrata.we evaluated the potential impact of caspofungin (cas) on the functional activities of polymorphonuclear leukocytes (pmns) from hemodialyzed patients (hds) and renal transplant recipients (rtrs) against a multidrug-resistant clinical strain of candida glabrata compared with those of pmns from healthy subjects (hss).201323834733
new pcr test for detection of candida glabrata based on the molecular target chosen by the rapd technique.rapid, reliable diagnosis is a necessary condition for the successful treatment of infections. such diagnostic assays are continually being developed. the paper presents a method for selecting the molecular target for pcr-based diagnostics based on the comparison of rapd patterns. a sequence encoding candida glabrata cbs138 hypothetical protein was selected. the limit of detection for pcr and real-time pcr reactions with dna extracted from blood samples spiked with candida glabrata was estimated ...201323829082
rapid emergence of echinocandin resistance in candida glabrata resulting in clinical and microbiologic failure.we report a case of candida glabrata candidemia that developed resistance to micafungin within 8 days of initiation of therapy in a patient without previous echinocandin exposure or other known risk factors for clinical or microbiological failure. pre- and postresistant isolates were confirmed to be isogenic, and sequencing of hot spots known to confer echinocandin resistance revealed a phenylalanine deletion at codon 659 within fks2.201323817368
microbial ethanol production in postmortem urine sample.we present a case in which postmortem blood ethanol concentration was 0.02 g/kg and acetone concentration was 0.51 g/kg, while urine ethanol concentration was 6.0 g/kg and acetone concentration was 0.63 g/kg. in the urine sample, sodium fluoride was not added. the urinary ethanol concentration continued to increase without any remarkable increase of isopropanol concentration and external contamination was excluded. species of bacteria and yeasts, including candida glabrata, were isolated from ur ...201323812407
the dual role of candida glabrata drug:h+ antiporter cgaqr1 (orf cagl0j09944g) in antifungal drug and acetic acid resistance.opportunistic candida species often have to cope with inhibitory concentrations of acetic acid, in the acidic environment of the vaginal mucosa. given that the ability of these yeast species to tolerate stress induced by weak acids and antifungal drugs appears to be a key factor in their persistence and virulence, it is crucial to understand the underlying mechanisms. in this study, the drug:h(+) antiporter cgaqr1 (orf cagl0j09944g), from candida glabrata, was identified as a determinant of resi ...201323805133
the pneumocystis ace2 transcription factor regulates cell wall-remodeling genes and organism virulence.pneumocystis carinii (pc) β-glucans are major components of the organism cell wall; yet, the regulation of pc cell wall genesis and remodeling is not well understood. ace2 transcription factors, which are present in many fungi, regulate glucanases and other enzymes needed for cell wall remodeling. the cloning and heterologous expression of pcace2 in ace2δ saccharomyces cerevisiae demonstrated that pcace2 can restore the defective glucanase and endochitinase gene expression of the mutant as well ...201323801335
antifungal activity of the noncytotoxic human peptide hepcidin 20 against fluconazole-resistant candida glabrata in human vaginal fluid.vaginal infections caused by candida glabrata are difficult to eradicate due to this species' scarce susceptibility to azoles. previous studies have shown that the human cationic peptide hepcidin 20 (hep-20) exerts fungicidal activity in sodium phosphate buffer against a panel of c. glabrata clinical isolates with different levels of susceptibility to fluconazole. in addition, the activity of the peptide was potentiated under acidic conditions, suggesting an application in the topical treatment ...201323796919
identification of fungi species in the onychomycosis of institutionalized elderly.superficial fungal infections are caused by dermatophytes, yeasts or filamentous fungi. they are correlated to the etiologic agent, the level of integrity of the host immune response, the site of the lesion and also the injured tissue.201723793195
antifungal activities of diphenyl diselenide alone and in combination with fluconazole or amphotericin b against candida glabrata.here, we evaluated combinations of diphenyl diselenide [(phse)2] with fluconazole and amphotericin b in a checkerboard assay against clinical candida glabrata strains. minimal inhibitory concentration (geometric mean) ranged from 0.25 to >64 (5.16 μg/ml) for (phse)2, 1 to 32 (5.04 μg/ml) for fluconazole and 0.06 to 0.5 (0.18 μg/ml) for amphotericin b. synergistic (76.66 %) and indifferent (23.34 %) interactions were observed for (phse)2 + amphotericin b combination. (phse)2 + fluconazole combina ...201323793863
[molecular biological approach to screening essential genes as potential targets for antifungal targets in pathogenic yeast candida].we established a system, named ets system, for screening and identification of essential genes from the pathogenic haploid yeast candida glabrata by using temperature-sensitive (ts) mutants. based on the general concepts that ts mutations are generated within essential genes in the genome by virtue of point mutation, the ets system enabled us to screen and identify a variety of essential genes from the c. glabrata genomic dna library as the genes that complement ts mutations. the ets system esta ...201323760075
yeast dynamics during spontaneous fermentation of mawè and tchoukoutou, two traditional products from benin.mawè and tchoukoutou are two traditional fermented foods largely consumed in benin, west africa. their preparations remain as a house art and they are the result of spontaneous fermentation processes. in this study, dynamics of the yeast populations occurring during spontaneous fermentations of mawè and tchoukoutou were investigated using both culture-dependent and -independent approaches. for each product, two productions were followed. samples were taken at different fermentation times and yea ...201323756236
[candidaemia by candida glabrata in a young patient with no previous symptoms]. 201323746706
metabolic engineering of torulopsis glabrata for malate production.the yeast torulopsis glabrata cctcc m202019, which is used for industrial pyruvate production, was chosen to explore the suitability of engineering this multi-vitamin auxotrophic yeast for increased malate production. various metabolic engineering strategies were used to manipulate carbon flux from pyruvate to malate: (i) overexpression of pyruvate carboxylase and malate dehydrogenase; (ii) identification of the bottleneck in malate production by model inx804; (iii) simultaneous overexpression o ...201323707987
prelog and anti-prelog stereoselectivity of two ketoreductases from candida glabrata.two ketoreductases from candida glabrata were used for the asymmetric reduction of prochiral substituted acetophenones displayed different enantiopreference toward para-, meta-substituted and ortho-halogen substituted acetophenones with excellent enantioselectivity. homology modeling and docking analysis were in conformity with this interested enantiopreference obtained from experimental tests. the reduction of a series of other substituted aryl ketones was also investigated using the two ketore ...201323690040
synthesis and biological evaluation of pyrazoline derivatives bearing an indole moiety as new antimicrobial agents.1-(p-methylphenyl)-3,5-diaryl-2-pyrazoline derivatives (2a-f) were synthesized via the treatment of 1-(1h-indol-3-yl)-3-aryl-2-propen-1-ones (1a-f) with p-methylphenylhydrazine hydrochloride in hot acetic acid. the structures of these compounds were elucidated by ir, ¹h nmr, and mass spectral data and elemental analysis. these compounds were investigated for their antimicrobial activity. brine-shrimp lethality assay was carried out to determine the toxicity of the compounds. compound 2e, which i ...201323681942
small chromosomes among danish candida glabrata isolates originated through different mechanisms.we analyzed 192 strains of the pathogenic yeast candida glabrata from patients, mainly suffering from systemic infection, at danish hospitals during 1985-1999. our analysis showed that these strains were closely related but exhibited large karyotype polymorphism. nine strains contained small chromosomes, which were smaller than 0.5 mb. regarding the year, patient and hospital, these c. glabrata strains had independent origin and the analyzed small chromosomes were structurally not related to eac ...201323670790
caspofungin mics correlate with treatment outcomes among patients with candida glabrata invasive candidiasis and prior echinocandin exposure.mutations in candida glabrata fks genes, which encode the echinocandin target enzyme, are independent risk factors for treatment failures during invasive candidiasis. we retrospectively compared the ability of caspofungin susceptibility testing methods to identify c. glabrata fks mutant isolates and predict outcomes among patients at our center. eight percent (10/120) of sterile-site c. glabrata isolates harbored fks1 (n = 3) or fks2 (n = 7) mutations, including 32% (10/32) recovered from patien ...201323669387
local silencing controls the oxidative stress response and the multidrug resistance in candida glabrata.in candida glabrata, the sirtuins sir2 and hst1 control the expression of a wide number of genes including adhesins required for host colonization and niacin transporters needed for growth. given that these sirtuins can be inactivated during infection, we asked if their inhibition could modify the response of c. glabrata to other stressful conditions. here, we found that deletion of hst1 decreases susceptibility of c. glabrata to fluconazole and hydrogen peroxide. the transcription factor pdr1 a ...201323651300
candida glabrata drug:h+ antiporter cgqdr2 confers imidazole drug resistance, being activated by transcription factor cgpdr1.the widespread emergence of antifungal drug resistance poses a severe clinical problem. though predicted to play a role in this phenomenon, the drug:h(+) antiporters (dha) of the major facilitator superfamily have largely escaped characterization in pathogenic yeasts. this work describes the first dha from the pathogenic yeast candida glabrata reported to be involved in antifungal drug resistance, the c. glabrata qdr2 (cgqdr2) gene (orf cagl0g08624g). the expression of cgqdr2 in c. glabrata was ...201323629708
synthesis and carbonic anhydrase inhibitory properties of sulfamides structurally related to dopamine.a series of novel sulfamides incorporating the dopamine scaffold were synthesized. reaction of amines and tert-butyl-alcohol/benzyl alcohol in the presence of chlorosulfonyl isocyanate (csi) afforded sulfamoyl carbamates, which were converted to the title compounds by treatment with trifluoroacetic acid or by palladium-catalyzed hydrogenolysis. inhibition of six α-carbonic anhydrases (cas, ec 4.2.1.1), that is, ca i, ca ii, ca va, ca ix, ca xii and ca xiv, and two β-cas from candida glabrata (cg ...201323623256
expression of neutral β-glucosidase from scytalidium thermophilum in candida glabrata for ethanol production from alkaline-pretreated rice straw.we successfully expressed the neutral β-glucosidase (bgl4) from scytalidium thermophilum in the thermotolerant yeast candida glabrata. compared to the strain expressing aspergillus acidic β-glucosidase (bgl1), the bgl4-expressing strain showed a higher cellobiose fermentation ability at ph 6.0 and 40°c, leading to a higher ethanol production from alkaline-pretreated rice straw.201323597919
a severe case of haemodynamic instability during anidulafungin administration.anidulafugin is an echinocandin used for the treatment of candida infections in non-neutropenic adults. echinocandins show few drug-drug interactions and are usually well tolerated. we report a case of acute hypotension, bradycardia and haemodynamic instability with consecutive cardiopulmonary resuscitation during anidulafungin administration.201323550735
caulerprenylols a and b, two rare antifungal prenylated para-xylenes from the green alga caulerpa racemosa.two new prenylated para-xylenes, named caulerprenylols a (1) and b (2), were isolated from the green alga caulerpa racemosa, collected from the zhanjiang coastline, china. the structures of the two metabolites were elucidated on the basis of detailed spectroscopic analysis. this is the first report of prenylated para-xylenes from marine algae and from marine organisms as well. moreover, caulerprenylol b (2) is also characterized by an uncommon indane ring system. in in vitro bioassays, the new c ...201323548547
candida nivariensis as an etiologic agent of vulvovaginal candidiasis in a tertiary care hospital of new delhi, india.candida nivariensis is a cryptic species, phenotypically indistinguishable from candida glabrata and identified by molecular methods. aside its isolation from broncho-alveolar lavage, we report for the first time the etiologic role of c. nivariensis in 4 patients with vulvovaginal candidiasis. of 100 phenotypically identified c. glabrata isolates originating from vaginal swabs, 4 were identified as c. nivariensis by polymerase chain reaction and confirmed by sequencing. all of the c. nivariensis ...201323537782
expression of pneumocystis jirovecii major surface glycoprotein in saccharomyces cerevisiae.the major surface glycoprotein (msg), which is the most abundant protein expressed on the cell surface of pneumocystis organisms, plays an important role in the attachment of this organism to epithelial cells and macrophages. in the present study, we expressed pneumocystis jirovecii msg in saccharomyces cerevisiae, a phylogenetically related organism. full-length p. jirovecii msg was expressed with a dna construct that used codons optimized for expression in yeast. unlike in pneumocystis organis ...201323532098
carbonic anhydrase inhibitors: inhibition of the β-class enzyme from the pathogenic yeast candida glabrata with sulfonamides, sulfamates and sulfamides.the fungal pathogen candida glabrata encodes for a β-carbonic anhydrase (ca, ec 4.2.1.1), cgnce103, recently discovered. only anions have been investigated as cgnce103 inhibitors up until now. here we report the first sulfonamides inhibition study of this enzyme. simple sulfonamides showed weak or moderate cgnce103 inhibitory properties, whereas acetazolamide, and a series of 4-substituted ureido-benzene-sulfonamides, sulfamates and sulfamides showed effective cgnce103 inhibitory properties, wit ...201323511020
the heme-binding protein dap1 links iron homeostasis to azole resistance via the p450 protein erg11 in candida glabrata.the pathogenic fungus candida glabrata is relatively resistant to azole antifungals, which target lanosterol 14α-demethylase (erg11p) in the ergosterol biosynthesis pathway. our study revealed that c. glabrata exhibits increased azole susceptibility under low-iron conditions. to investigate the molecular basis of this phenomenon, we generated a strain lacking the heme (iron protoporphyrin ix)-binding protein dap1 in c. glabrata. the δdap1 mutant displayed growth defects under iron-limited condit ...201323496820
candida glabrata and fks mutations: witnessing the emergence of the true multidrug-resistant candida. 201323487384
increasing echinocandin resistance in candida glabrata: clinical failure correlates with presence of fks mutations and elevated minimum inhibitory concentrations.fluconazole (flc) resistance is common in c. glabrata and echinocandins are often used as first-line therapy. resistance to echinocandin therapy has been associated with fks1 and fks2 gene alterations.201323487382
echinocandins: production and applications.the first echinocandin-type antimycotic (echinocandin b) was discovered in the 1970s. it was followed by the isolation of more than 20 natural echinocandins. these cyclic lipo-hexapeptides are biosynthesized on non-ribosomal peptide synthase complexes by different ascomycota fungi. they have a unique mechanism of action; as non-competitive inhibitors of β-1,3-glucan synthase complex they target the fungal cell wall. results of the structure-activity relationship experiments let us develop semisy ...201323463246
gain-of-function mutations in pdr1, a regulator of antifungal drug resistance in candida glabrata, control adherence to host cells.candida glabrata is an emerging opportunistic pathogen that is known to develop resistance to azole drugs due to increased drug efflux. the mechanism consists of cgpdr1-mediated upregulation of atp-binding cassette transporters. a range of gain-of-function (gof) mutations in cgpdr1 have been found to lead not only to azole resistance but also to enhanced virulence. this implicates cgpdr1 in the regulation of the interaction of c. glabrata with the host. to identify specific cgpdr1-regulated step ...201323460523
role of glutathione in the oxidative stress response in the fungal pathogen candida glabrata.candida glabrata, an opportunistic fungal pathogen, accounts for 18-26 % of all candida systemic infections in the us. c. glabrata has a robust oxidative stress response (osr) and in this work we characterized the role of glutathione (gsh), an essential tripeptide-like thiol-containing molecule required to keep the redox homeostasis and in the detoxification of metal ions. gsh is synthesized from glutamate, cysteine, and glycine by the sequential action of gsh1 (γ-glutamyl-cysteine synthetase) a ...201323455613
the candida glabrata sterol scavenging mechanism, mediated by the atp-binding cassette transporter aus1p, is regulated by iron limitation.during disseminated infection by the opportunistic pathogen candida glabrata, uptake of sterols such as serum cholesterol may play a significant role during pathogenesis. the atp-binding cassette transporter aus1p is thought to function as a sterol importer and in this study, we show that uptake of exogenous sterols occurred under anaerobic conditions in wild-type cells of c. glabrata but not in aus1-deleted mutant (aus1δ) cells. in aerobic cultures, growth inhibition by fluconazole was prevente ...201323448689
transcriptional profiling of candida glabrata during phagocytosis by neutrophils and in the infected mouse spleen.expression microarray analysis of candida glabrata following phagocytosis by human neutrophils was performed, and results were compared with those from c. glabrata incubated under conditions of carbohydrate or nitrogen deprivation. twenty genes were selected to represent the major cell processes altered by phagocytosis or nutrient deprivation. quantitative real-time pcr (qrt-pcr) with taqman chemistry was used to assess expression of the same genes in spleens of mice infected intravenously with ...201323403555
sir3 polymorphisms in candida glabrata clinical isolates.the opportunistic fungal pathogen candida glabrata adheres tightly to epithelial cells in culture, mainly through the adhesin epa1. epa1 is the founding member of a family of up to 23 putative adhesin-encoding genes present in the c. glabrata genome. the majority of the epa genes are localized close to the telomeres, where they are repressed by subtelomeric silencing that depends on the sir, ku, rif1, and rap1 proteins. epa6 and epa7 also encode functional adhesins that are repressed in vitro. e ...201323392823
dissection of ire1 functions reveals stress response mechanisms uniquely evolved in candida glabrata.proper protein folding in the endoplasmic reticulum (er) is vital in all eukaryotes. when misfolded proteins accumulate in the er lumen, the transmembrane kinase/endoribonuclease ire1 initiates splicing of hac1 mrna to generate the bzip transcription factor hac1, which subsequently activates its target genes to increase the protein-folding capacity of the er. this cellular machinery, called the unfolded protein response (upr), is believed to be an evolutionarily conserved mechanism in eukaryotes ...201323382685
intrauterine fetal loss associated with candida glabrata chorioamnionitis: report of two cases.chorioamnionitis is most commonly the result of an ascending infection caused by bacteria found within the lower genital tract. yeast infections causing chorioamnionitis are very uncommon. candida glabrata is a yeast that is considered to be a commensal of the vagina but vaginitis and rarely upper genital tract infection have been described. we report two cases of fungal chorioamnionitis occurring in pregnancies with a history of in vitro fertilization and cervical cerclage, both resulting in fe ...201323354803
overexpression of aldo-keto-reductase in azole-resistant clinical isolates of candida glabrata determined by cdna-aflp. 201323351326
differential expression of the candida glabrata cgrta1 and cgrsb1 genes in response to various stress conditions.candida glabrata, a human opportunistic pathogen is characterized by intrinsic, low susceptibility to fluconazole and a high capacity for acquiring high-level azole resistance. this is related to the elevated expression of genes belonging to the cgpdr1-governed regulon, comprising numerous genes, of which the multidrug abc transporter-encoding cgcdr1, cgcdr2, cgsnq2 are the best characterized. the function of certain pdr loci, such as cgrta1 and cgrsb1 is poorly understood. these are homologs of ...201323337499
serum cholesterol promotes the growth of candida glabrata in the presence of fluconazole.the pathogenic fungus candida glabrata is thought to utilize extracellular sterols during infection, but there have been few reports on the sterol uptake mechanisms of this fungus. the addition of serum promoted the growth of c. glabrata cells in the presence of the sterol inhibitor fluconazole, probably as the result of incorporation of cholesterol from serum. we demonstrated that lipoprotein-deficient serum, in which most of the cholesterol was eliminated, could not rescue the growth of flucon ...201323233084
stb5 is a negative regulator of azole resistance in candida glabrata.the opportunistic yeast pathogen candida glabrata is recognized for its ability to acquire resistance during prolonged treatment with azole antifungals (j. e. bennett, k. izumikawa, and k. a. marr. antimicrob. agents chemother. 48:1773-1777, 2004). resistance to azoles is largely mediated by the transcription factor pdr1, resulting in the upregulation of atp-binding cassette (abc) transporter proteins and drug efflux. studies in the related yeast saccharomyces cerevisiae have shown that pdr1p fo ...201323229483
fluconazole versus an echinocandin for candida glabrata fungaemia: a retrospective cohort study.we studied whether fluconazole or echinocandin treatment of candida glabrata fungaemia results in superior outcomes.201323212115
milbemycins: more than efflux inhibitors for fungal pathogens.existing antifungal agents are still confronted to activities limited to specific fungal species and to the development of resistance. several improvements are possible either by tackling and overcoming resistance or exacerbating the activity of existing antifungal agents. in candida glabrata, azole resistance is almost exclusively mediated by abc transporters (including c. glabrata cdr1 [cgcdr1] and cgcdr2) via gain-of-function mutations in the transcriptional activator cgpdr1 or by mitochondri ...201323208712
reconstruction and analysis of the genome-scale metabolic network of candida glabrata.candida glabrata has been recognized as an efficient industrial microorganism for the production of pyruvate, the most widely used α-oxocarboxylic acid in the areas of agrochemicals, drugs, and chemicals. to gain a comprehensive understanding of its physiology and cellular metabolism, the genome-scale metabolic model for c. glabrata (named inx804), comprising 804 genes, 1287 reactions, and 1025 metabolites, was reconstructed by genome sequence annotation and biochemical data mining. the flux bal ...201323172360
candiduria in haematologic malignancy patients without a urinary catheter: nothing more than a frailty marker?there is scarcity of data regarding significance of candiduria in patients with haematologic malignancies and its association with invasive candidiasis. to that end, we retrospectively evaluated all hospitalised, non-intensive care unit patients with haematologic malignancies and candiduria during a 10-year period (2001-2011). to decrease the possibility of bladder colonisation and sample contamination, we excluded all patients with candiduria who had urinary catheters and those with concomitant ...201323170870
chemical composition and biological activities of essential oil from hyptis crenata growing in the brazilian cerrado.essential oils from species of the genus hyptis are well-known for their significant biological properties, including antimicrobial and acaricidal activities. the essential oil from the aerial parts of h. crenata was obtained by hydrodistillation; bomeol (17.8%), 1,8-cineol (15.6%) and p-cimene (7.9%) were characterized by gc-ms as its major constituents. the essential oil was evaluated in vitro for its antimicrobial activities against six fungal and five bacterial strains, by measuring the resp ...201223157018
candida glabrata sepsis associated with chorioamnionitis in an in vitro fertilization pregnancy: case report and review.we report a case of candida glabrata sepsis associated with chorioamnionitis in an in vitro fertilization-assisted pregnancy. there is a strong association between c. glabrata chorioamnionitis and assisted fertility techniques. candida glabrata chorioamnionitis presents unique management challenges.201323143095
isopcr: an analytically sensitive, nested, multiplex nucleic acid amplification method.nucleic acid tests that can simultaneously detect multiple targets with high sensitivity, specificity, and speed are highly desirable. to meet this need, we developed a new approach we call the isopcr method.201323115058
evaluation of caspofungin susceptibility testing by the new vitek 2 ast-ys06 yeast card using a unique collection of fks wild-type and hot spot mutant isolates, including the five most common candida species.fks mutant isolates associated with breakthrough or failure cases are emerging in clinical settings. discrimination of these from wild-type (wt) isolates in a routine laboratory setting is complicated. we evaluated the ability of caspofungin mic determination using the new vitek 2 ast-y06 yeast susceptibility card to correctly identify the fks mutants from wt isolates and compared the performance to those of the clsi and eucast reference methods. a collection of 98 candida isolates, including 31 ...201323089746
mutants in the candida glabrata glycerol channels are sensitized to cell wall stress.many fungal species use glycerol as a compatible solute with which to maintain osmotic homeostasis in response to changes in external osmolarity. in saccharomyces cerevisiae, intracellular glycerol concentrations are regulated largely by the high osmolarity glycerol (hog) response pathway, both through induction of glycerol biosynthesis and control of its flux through the plasma membrane fps1 glycerol channel. the channel activity of fps1 is also controlled by a pair of positive regulators, rgc1 ...201223087370
neck rotation and neck mimic docking in the noncatalytic kar3-associated protein vik1.kar3vik1 is a heterodimeric kinesin with one catalytic subunit (kar3) and one noncatalytic subunit (vik1).201223043140
structural basis for promiscuity and specificity during candida glabrata invasion of host epithelia.the human pathogenic yeast candida glabrata harbors more than 20 surface-exposed, epithelial adhesins (epas) for host cell adhesion. the epa family recognizes host glycans and discriminates between target tissues by their adhesin (a) domains, but a detailed structural basis for ligand-binding specificity of epa proteins has been lacking so far. in this study, we provide high-resolution crystal structures of the epa1a domain in complex with different carbohydrate ligands that reveal how host cell ...201223035251
two clinical isolates of candida glabrata exhibiting reduced sensitivity to amphotericin b both harbor mutations in erg2.two novel isolates of candida glabrata exhibiting reduced sensitivity to amphotericin b (mic, 8 μg ml(-1)) were found to be erg2 mutants, wherein δ(8)-sterol intermediates comprised >90% of the total cellular sterol fraction. both harbored an alteration at thr(121) in erg2; the corresponding residue (thr(119)) in saccharomyces cerevisiae is essential for sterol δ8-δ7 isomerization. this constitutes the first report of c. glabrata harboring mutations in erg2 and exhibiting reduced sensitivity to ...201223027188
candida glabrata: an unusual fungal infection following a total hip replacement.a 60-year-old woman, after a femoral neck fracture and joint replacement, underwent a girdlestone's procedure and received aggressive antimicrobial therapy in order to completely eradicate the fungal infection candida glabrata. in the majority of such cases, a revised hip arthroplasty would be considered following debridement. however, due to the recurrence of this infection and a key associated risk factor, radical removal with concurrent drug therapy was the only option.201223008369
distribution of fluconazole-resistant candida bloodstream isolates among hospitals and inpatient services in israel.the emergence of fluconazole-resistant candida (frc) is worrisome, but little is known about susceptibility patterns in different nosocomial settings. we prospectively analysed candida bloodstream isolates in 18 medical centres in israel (six tertiary-care and 12 community hospitals). the study included 444 episodes of candidaemia (450 patient-specific isolates, 8.5% fluconazole-resistant). institutional frc bloodstream infection rates correlated with annual inpatient days, and were strongly ass ...201323005038
fluconazole resistance in candida glabrata is associated with increased bud formation and metallothionein production.virulence associated with fluconazole (fl) resistance in candida glabrata is a global problem and has not been well characterized at the proteome level. in this study, a stable fl-resistant (mic >256 µg ml(-1)) strain of c. glabrata was generated on agar containing fl. eight phenotypic mutants were characterized by contour-clamped homogeneous electrophoretic field analysis and two-dimensional page. the secondary derivatives of c. glabrata yielded four distinct genotypes with varying chromosomal ...201323002065
optimizing echinocandin dosing and susceptibility breakpoint determination via in vivo pharmacodynamic evaluation against candida glabrata with and without fks mutations.echinocandins are a preferred therapy for invasive candidiasis due to their potency and broad spectrum. resistance, especially in candida glabrata, is an emerging threat to their use. pharmacodynamic (pd) studies examining reduced susceptibility secondary to fks mutations in c. glabrata are lacking. the current study explored pd targets for anidulafungin, caspofungin, and micafungin in an in vivo invasive candidiasis model against 11 c. glabrata isolates with known or putative fks mutations. the ...201222948870
de novo generation of a phosphate starvation-regulated promoter in candida glabrata.what steps are required for a promoter to acquire regulation by an environmental condition? we address this question by examining a promoter in candida glabrata that is regulated by phosphate starvation and the transcription factor pho4. the gene pmu2 encodes a secreted acid phosphatase that resulted from gene duplication events not present in other ascomycetes, and only this gene of the three paralogs has acquired pho4 regulation. we observe that the pmu2 promoter from c. glabrata is not functi ...201222938599
[candida glabrata : pathogenicity and therapy update].chronic recurrent vulvovaginal candidiasis caused by candida glabrata is still rare in comparison to c. albicans infection, but therapy remains more difficult. standard agents as fluconazole or itraconazole often fail, as well as the newer systemic triazoles like voriconazole or posaconazole. micafungin is a new echinocandin drug with a wide antifungal spectrum including rare candida species. no clinical trials with micafungin in chronic recurrent vulvovaginal candidiasis have been undertaken. w ...201222925897
functional genomic analysis of candida glabrata-macrophage interaction: role of chromatin remodeling in virulence.fungal septicemia is an increasingly common complication of immunocompromised patients worldwide. candida species are the leading cause of invasive mycoses with candida glabrata being the second most frequently isolated candida species from intensive care unit patients. despite its clinical importance, very little is known about the mechanisms that c. glabrata employs to survive the antimicrobial and immune response of the mammalian host. here, to decipher the interaction of c. glabrata with the ...201222916016
crs-mis in candida glabrata: sphingolipids modulate echinocandin-fks interaction.infections with the azole-refractory yeast candida glabrata are now commonly treated with the echinocandins caspofungin (csf) or micafungin (mcf). true resistance (>  32-fold decreased susceptibility) to these lipopeptide inhibitors of cell wall synthesis is rare and strictly associated with mutations in integral membrane proteins fks1 or fks2. in contrast, mutants exhibiting 4- to 32-fold csf reduced susceptibility (crs) were readily selected in vitro, and surprisingly demonstrated 4- to 32-fol ...201222909030
changes in incidence and antifungal drug resistance in candidemia: results from population-based laboratory surveillance in atlanta and baltimore, 2008-2011.candidemia is common and associated with high morbidity and mortality; changes in population-based incidence rates have not been reported.201222893576
[efficacy of voriconazole treatment in chronic vulvovaginal candidosis due to candida glabrata].vulvovaginal candidosis is a common infection in young women, and it is associated with high morbidity and high health costs.201322885618
rapid identification of histoplasma capsulatum directly from cultures by multiplex pcr.the multiplex pcr developed from a suspension of the yeast fungi correctly identified fifty-one clinical of h. capsulatum var. capsulatum strains isolated from clinical samples and soil specimens. the multiplex pcr was developed by combining two pairs of primers, one of them was specific to the h. capsulatum and the other one, universal for fungi, turned out to be specific to h. capsulatum, regardless of the fungus isolate studied. primers designed to amplify a region of about 390-bp (hc i-hc ii ...201222821346
in vitro adhesion of candida glabrata to denture base acrylic resin modified by glow-discharge plasma treatment.this study evaluated the potential of plasma treatments to modify the surface chemistry and hydrophobicity of a denture base acrylic resin to reduce the candida glabrata adhesion. specimens (n = 54) with smooth surfaces were made and divided into three groups (n = 18): control - non-treated; experimental groups - submitted to plasma treatment (ar/50 w; aat/130 w). the effects of these treatments on chemical composition and surface topography of the acrylic resin were evaluated. surface free ener ...201322809146
determination of the effect of nd:yag laser irradiation through dentinal tubules on several oral pathogens.the effects of nd:yag laser irradiations at different power settings on several oral pathogens were evaluated. a total of 252 dentin samples were divided into seven groups consisting of 36 dentin specimens each. in each group, 9 of the 36 specimens were used as controls, thereby including a control in every group. the remaining 27 specimens were divided into three subgroups consisting of nine specimens according to different nd:yag laser settings (1.5, 1.8, and 2 w). each group was inoculated on ...201322767323
candida glabrata: an emerging pathogen in brazilian tertiary care hospitals.candida glabrata is an infrequent cause of candidemia in brazilian public hospitals. we investigated putative differences in the epidemiology of candidemia in institutions with different sources of funding. prospective laboratory-based surveillance of candidemia was conducted in seven private and two public brazilian tertiary care hospitals. among 4,363 episodes of bloodstream infection, 300 were caused by candida spp. (6.9%). incidence rates were significantly higher in public hospitals, i.e., ...201322762208
the presence of an fks mutation rather than mic is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to candida glabrata.echinocandins are frontline agents against invasive candidiasis (ic), but predictors for echinocandin therapeutic failure have not been well defined. mutations in candida fks genes, which encode the enzyme targeted by echinocandins, result in elevated mics and have been linked to therapeutic failures. in this study, echinocandin mics by broth microdilution and fks1 and fks2 mutations among c. glabrata isolates recovered from patients with ic at our center were correlated retrospectively with ech ...201222751546
evaluation of reference genes for real-time quantitative pcr studies in candida glabrata following azole treatment.the selection of stable and suitable reference genes for real-time quantitative pcr (rt-qpcr) is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. the present study aimed to identify reference genes as internal controls for gene expression studies by rt-qpcr in azole-stimulated candida glabrata.201222747760
occurrence of killer candida glabrata clinical isolates.in this work we characterized the occurrence of killer activity in 64 candida glabrata clinical isolates under different conditions. we found that only 6.25 % of the clinical isolates tested were positive for killer activity against a saccharomyces cerevisiae w303 sensitive strain. sensitivity of killer activity to different values of ph and temperatures was analyzed. we found that the killer activity presented by all isolates was resistant to every ph and temperature tested, although optimal ac ...201224031902
primary retroperitoneal abscess caused by candida glabrata.clinically, retroperitoneal abscesses present insidiously and the diagnosis may be delayed. this, with inadequate drainage, may result in increased morbidity and mortality. most cases result from a renal or gastrointestinal process, but in a small number of patients there is no identifiable source and the abscess is designated as "primary." most retroperitoneal abscesses are polymicrobial, and cultures often reveal organisms such as proteus mirabilis, staphylococcus species, peptostreptococcus, ...201222739567
occurrence of killer yeasts in isolates of clinical origin.a total of 1 025 strains belonging to different candida species of clinical origin were evaluated for their killer activity against sensitive strains of saccharomyces cerevisiae. isolates were identified by standard morphological and biochemical analyses. for the evaluation of the killer activity, potential killer isolates were streaked on plates previously seeded with the sensitive strain. a total of 52 candida isolates (5%) exhibited killer activity against both sensitive yeast strains. the oc ...201222735852
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