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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
sorbic acid stress activates the candida glabrata high osmolarity glycerol map kinase pathway.weak organic acids such as sorbic acid are important food preservatives and powerful fungistatic agents. these compounds accumulate in the cytosol and disturb the cellular ph and energy homeostasis. candida glabrata is in many aspects similar to saccharomyces cerevisiae. however, with regard to confrontation to sorbic acid, two of the principal response pathways behave differently in c. glabrata. in yeast, sorbic acid stress causes activation of many genes via the transcription factors msn2 and ...201324324463
treatment of fungal disease in the setting of neutropenia.invasive fungal infections are important causes of morbidity and attributable mortality in neutropenic patients with hematological malignancies, myelodysplasia, and aplastic anemia. successful risk-based strategies can be implemented for prophylaxis, empirical therapy, and preemptive therapy for the prevention and early treatment of invasive fungal infections in neutropenic hosts. the use of echinocandins for invasive candidiasis and voriconazole for invasive aspergillosis has significantly impr ...201324319214
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
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
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
[candida peritonitis in a haemodynamically stable patient. first choice of antifungal treatment … fluconazole?].candida peritonitis in postoperative patients is an independent predictor of mortality. empirical early antifungal therapy should be started in these patients, since according to the results of studies in patients with candidemia, this has an impact on the prognosis. the treatment recommended by clinical practice guidelines in patients with haemodynamic instability are candins, but they do not make explicit recommendations for patients with dysfunction of other organs, or high lactate levels.201322463782
proteomic analysis of intracellular and membrane proteins from voriconazole-resistant candida glabrata.the proteomic analysis of voriconazole resistant candida glabrata strain has not yet been investigated. in this study, differentially expressed proteins of intracellular and membrane fraction from voriconazole-susceptible, susceptible dose-dependent (s-dd), resistant c. glabrata strains were compared with each other and several proteins were identified.201324524017
establishment of an in vitro system to study intracellular behavior of candida glabrata in human thp-1 macrophages.a cell culture model system, if a close mimic of host environmental conditions, can serve as an inexpensive, reproducible and easily manipulatable alternative to animal model systems for the study of a specific step of microbial pathogen infection. a human monocytic cell line thp-1 which, upon phorbol ester treatment, is differentiated into macrophages, has previously been used to study virulence strategies of many intracellular pathogens including mycobacterium tuberculosis. here, we discuss a ...201324378622
candida nivariensis isolated from a renal transplant patient with persistent candiduria-molecular identification using its pcr and maldi-tof.we report on the isolation of candida nivariensis from a renal transplant patient with persistent candiduria. biochemical profiling misidentified isolates as candida glabrata (3/5) and candida inconspicua (2/5). all isolates produced white colonies on chromagar(™) candida medium. internal transcribed spacer (its) ribosomal gene sequence analysis and maldi-tof-ms analysis (bruker biotyper(™) 2.0) identified all isolates as c. nivariensis, demonstrating the utility of maldi-tof as a rapid, accurat ...201324432244
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
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
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
[first case report of catheter-related fungemia by candida nivariensis in the iberian peninsula].in recent years the incidence of candidemia caused by non-albicans candida species has been increasing. two cryptic species have been described within the candida glabrata complex, candida nivariensis and candida bracarensis, which may be troublesome in laboratory identification and have lower susceptibility to fluconazole.201322982698
rapid and accurate identification of isolates of candida species by melting peak and melting curve analysis of the internally transcribed spacer region 2 fragment (its2-mca).rapid identification of clinically important yeasts can facilitate the initiation of anti-fungal therapy, since susceptibility is largely species-dependent. we evaluated melting peak and melting curve analysis of the internally transcribed spacer region 2 fragment (its2-mca) as an identification tool for distinguishing between 16 candida spp., i.e. candida albicans, candida bracarensis, candida dubliniensis, candida famata, candida glabrata, candida guilliermondii, candida inconspicua, candida k ...201323142490
1-alkyl-(n,n-dimethylamino)pyridinium bromides: inhibitory effect on virulence factors of candida albicans and on the growth of bacterial pathogens.a homologous series of 1-alkyl-(n,n-dimethylamino)pyridinium bromides, termed compounds 1-11, was synthesized and studied for antibacterial and antifungal activity. of these, compound 8, containing a ten-carbon alkyl chain, showed maximum inhibition against all the tested bacterial strains. the highest antibacterial activity using a disc diffusion method was recorded against mycobacterium smegmatis [zone of inhibition (zoi): 45.75±0.25 mm], followed by escherichia coli, proteus mirabilis, vibrio ...201323118472
invasive candidiasis in pakistan: clinical characteristics, species distribution and antifungal susceptibility.this study reports for the first time, to our knowledge, descriptive epidemiological data for 188 invasive candida isolates from pakistan, including species identification and antifungal susceptibility against fluconazole, itraconazole, voriconazole, caspofungin, micafungin, anidulafungin and amphotericin. risk factors for invasive candidiasis (ic) were determined for 96 patients from karachi, pakistan. in adults and neonates, candida tropicalis (38 and 36 %, respectively) was the most common sp ...201323105021
elevated chitin content reduces the susceptibility of candida species to caspofungin.the echinocandin antifungal drugs inhibit synthesis of the major fungal cell wall polysaccharide β(1,3)-glucan. echinocandins have good efficacy against candida albicans but reduced activity against other candida species, in particular candida parapsilosis and candida guilliermondii. treatment of candida albicans with a sub-mic level of caspofungin has been reported to cause a compensatory increase in chitin content and to select for sporadic echinocandin-resistant fks1 point mutants that also h ...201323089748
candidacidal effect of fluconazole and chlorhexidine released from acrylic polymer.to investigate the efficacy and rate of killing of a fluconazole- or chlorhexidine-impregnated polymeric delivery system against fluconazole-susceptible and -resistant candida albicans and fluconazole-resistant candida glabrata.201323171950
effect of different pre-irradiation times on curcumin-mediated photodynamic therapy against planktonic cultures and biofilms of candida spp.the aim of this study was to evaluate the effects of pre-irradiation time (pit) on curcumin (cur)-mediated photodynamic therapy (pdt) against planktonic and biofilm cultures of reference strains of candida albicans, candida glabrata and candida dubliniensis.201323153629
the drosophila toll pathway controls but does not clear candida glabrata infections.the pathogenicity of candida glabrata to patients remains poorly understood for lack of convenient animal models to screen large numbers of mutants for altered virulence. in this study, we explore the minihost model drosophila melanogaster from the dual perspective of host and pathogen. as in vertebrates, wild-type flies contain c. glabrata systemic infections yet are unable to kill the injected yeasts. as for other fungal infections in drosophila, the toll pathway restrains c. glabrata prolifer ...201323401590
[genotyping of vaginal candida glabrata isolates using microsatellite marker analysis and dna sequencing to identify mutations associated with antifungal resistance].vulvovaginal candidosis is the second most common cause of vaginitis (17-39%) after bacterial vaginosis (22-50%). since the diagnosis of vulvovaginal candidosis mainly depends on clinical findings without mycologic confirmatory tests and treated empirically, the actual incidence rate of vulvovaginal candidosis is unknown. approximately 70-90% of vulvovaginal candidosis cases are caused by candida albicans, however the increasing incidence of c.glabrata infections and its reduced susceptibility t ...201323390908
intracellular ph homeostasis in candida glabrata in infection-associated conditions.candida glabrata is an opportunistic fungal pathogen which is a growing concern for immunocompromised patients. it is ranked as the second most common cause of candidiasis after candida albicans. for pathogenic yeasts, intracellular ph (phi) has been implicated in proliferation, dimorphic switching and virulence. we expressed the ph-sensitive green fluorescent protein variant ratiometric phluorin in the cytosol of c. glabrata to study phi dynamics in living cells. we evaluated the response of ph ...201323378571
structural analysis of the active sites of dihydrofolate reductase from two species of candida uncovers ligand-induced conformational changes shared among species.a novel strategy for targeting the pathogenic organisms candida albicans and candida glabrata focuses on the development of potent and selective antifolates effective against dihydrofolate reductase. crystal structure analysis suggested that an essential loop at the active site (thr 58-phe 66) differs from the analogous residues in the human enzyme, potentially providing a mechanism for achieving selectivity. in order to probe the role of this loop, we employed chemical synthesis, crystal struct ...201323375226
preparation and characterization of mucoadhesive thermoresponsive systems containing propolis for the treatment of vulvovaginal candidiasis.this work describes the preparation and characterization of mucoadhesive thermoresponsive systems consisted of poloxamer 407 (p407), carbopol® 934p (c934p), and propolis to treat vulvovaginal candidiasis (vvc). systems were obtained with different percentages of p407 and c934p to deliver propolis, a potent drug against vvc. temperature of gelation, hardness, compressibility, adhesiveness, elasticity, cohesiveness, mucoadhesion, rheology (continuous flow and oscillatory), in vitro drug release, a ...201323334938
candidaemia in sweden: a nationwide prospective observational survey.a prospective observational nationwide investigation was performed from september 2005 to august 2006 to study the epidemiology of candidaemia in sweden. from 385 patients, 403 isolates were recovered, yielding an incidence of 4.2 cases per 100 000 inhabitants. candida albicans was the most common species (61%), followed by candida glabrata (20%) and candida parapsilosis (9%). the rates of resistance to fluconazole were ≤ 1% in c. albicans and 6-29% in non-albicans species other than c. glabrata ...201323331511
microbiology and epidemiology of oral yeast colonization in hemopoietic progenitor cell transplant recipients.we monitored the epidemiology and microbiology of oral yeast colonization in patients undergoing hemopoietic progenitor cell transplantation (hpct) to examine associations between yeast colonization and oral mucositis.201323312542
the telomere capping complex cst has an unusual stoichiometry, makes multipartite interaction with g-tails, and unfolds higher-order g-tail structures.the telomere-ending binding protein complex cst (cdc13-stn1-ten1) mediates critical functions in both telomere protection and replication. we devised a co-expression and affinity purification strategy for isolating large quantities of the complete candida glabrata cst complex. the complex was found to exhibit a 2∶4∶2 or 2∶6∶2 stoichiometry as judged by the ratio of the subunits and the native size of the complex. stn1, but not ten1 alone, can directly and stably interact with cdc13. in gel mobil ...201323300477
a risk factor analysis of healthcare-associated fungal infections in an intensive care unit: a retrospective cohort study.the incidence of fungal healthcare-associated infection (hai) has increased in a major teaching hospital in the northern part of taiwan over the past decade, especially in the intensive care units (icus). the purpose of this study was to determine the factors that were responsible for the outbreak and trend in the icu.201323298156
oral candida species in head and neck cancer patients treated by radiotherapy.this paper aimed to identify and quantify candida on head and neck irradiated patients with two comparative elderly populations.201323260345
silver colloidal nanoparticles: effect on matrix composition and structure of candida albicans and candida glabrata biofilms.the aim of this study was to assess the effect of different silver nanoparticles (sn) concentrations on the matrix composition and structure of candida albicans and candida glabrata biofilms.201323231706
activity of mk-3118, a new oral glucan synthase inhibitor, tested against candida spp. by two international methods (clsi and eucast).to evaluate the activity of the orally bioavailable enfumafungin derivative mk-3118 and comparator antifungal agents tested against a collection of 113 clinical isolates of candida spp. using clsi and eucast broth microdilution (bmd) methods.201323190764
impact of imipenem treatment on colonic mycobiota in rats with double-hit sepsis.broad-spectrum antibiotic administration promotes intestinal colonization of exogenous fungal pathogens in healthy animals and has been recognized as one of the risk factors of invasive fungal infection in clinical settings. it is unclear whether broad-spectrum antibiotic treatment would change the intestinal mycobiota without exogenous fungal challenge in the context of sepsis.201323673098
investigation of the function of candida albicans als3 by heterologous expression in candida glabrata.during hematogenously disseminated infection, blood-borne candida albicans invades the endothelial cell lining of the vasculature to invade the deep tissues. although the c. albicans als3 invasin is critical for invasion and damage of endothelial cells in vitro, a c. albicans als3δ/δ mutant has normal virulence in the mouse model of disseminated infection. we hypothesized that the contribution of als3 to virulence is obscured by the presence of additional c. albicans invasins. to elucidate the i ...201323630968
candida glabrata olecranon bursitis treated with bursectomy and intravenous caspofungin.orthopedic surgeons are becoming more involved in the care of patients with septic arthritis and bursitis caused by yeast species. this case report involves a middle-aged immunocompromised female who developed a candida glabrata septic olecranon bursitis that developed after she received a corticosteroid injection in the olecranon bursa for presumed aseptic bursitis. candida (torulopsis) glabrata is the second most frequently isolated candida species from the bloodstream in the united states. in ...201323628576
histatin 5 resistance of candida glabrata can be reversed by insertion of candida albicans polyamine transporter-encoding genes dur3 and dur31.candida albicans and candida glabrata are predominant fungi associated with oral candidiasis. histatin 5 (hst 5) is a small cationic human salivary peptide with high fungicidal activity against c. albicans, however many strains of c. glabrata are resistant. since hst 5 requires fungal binding to cell wall components prior to intracellular translocation, reduced hst 5 binding to c. glabrata may be the reason for its insensitivity. c. glabrata has higher surface levels of β-1,3-glucans as compared ...201323613860
epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme.significant changes in the management of fungaemia have occurred over the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. these changes may impact the epidemiology of fungaemia. we present nationwide data for denmark from 2010 to 2011. a total of 1081 isolates from 1047 episodes were recorded in 995 patients. the numbers of patients, episodes and recovered isolates increased by 13.1%, 14.5% and 14 ...201323607326
synthesis and antimicrobial activity of novel amphiphilic aromatic amino alcohols.we report in this work the preparation and in vitro antimicrobial evaluation of novel amphiphilic aromatic amino alcohols synthesized by reductive amination of 4-alkyloxybenzaldehyde with 2-amino-2-hydroxymethyl-propane-1,3-diol. the antibacterial activity was determined against four standard strains (staphylococcus aureus, staphylococcus epidermidis, escherichia coli, pseudomonas aeruginosa) and 21 clinical isolates of methicillin-resistant staphylococcus aureus. the antifungal activity was eva ...201323587426
the efficacy and safety of sertaconazole cream (2 %) in diaper dermatitis candidiasis.diaper dermatitis (dd) is an inflammatory irritating condition that is common in infants. most cases are associated with the yeast colonization of candida or diaper dermatitis candidiasis (ddc), and therefore, the signs and symptoms improve with antimycotic treatment. sertaconazole is a broad-spectrum third-generation imidazole derivative that is effective and safe for the treatment for superficial mycoses, such as tineas, candidiasis, and pityriasis versicolor. our goal was to assess the effica ...201323546772
species distribution and virulence factors of candida spp. isolated from the oral cavity of kidney transplant recipients in brazil.although yeasts belonging to the genus candida are frequently seen as commensals in the oral cavity, they possess virulence attributes that contribute for pathogenicity. the aims of the present study were to study the prevalence of candida spp. isolated from the oral cavity of renal transplant recipients and to analyze strains virulence factors. we isolated a total of 70 candida strains from 111 transplant recipients, and candida albicans was the most prevalent species (82.86 %). oral candidiasi ...201323539354
candidemia among adults in soweto, south africa, 1990-2007.studies on candidemia occurring among adults in southern african are limited. we aimed to document the epidemiology of candidemia among adults in soweto.201323535300
epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in italy and spain.candidemia has become an important bloodstream infection that is frequently associated with high rates of mortality and morbidity, and its growing incidence is related to complex medical and surgical procedures. we conducted a multicenter study in five tertiary care teaching hospitals in italy and spain and evaluated the epidemiology, species distribution, antifungal susceptibilities, and outcomes of candidemia episodes. in the period of 2008 to 2010, 995 episodes of candidemia were identified i ...201324108614
effects of bovine lactoferrin to oral candida albicans and candida glabrata isolates recovered from the saliva in elderly people.the effects of bovine lactoferrin (blf) on the growth of candida species and on inflammatory cytokine production in gingival keratinocytes, ndusd-1 co-cultured with candida strains were investigated. the results showed that blf at 10 and 100 μg/ml significantly inhibits the growth of two c. albicans strains and two c. glabrata strains isolated from the saliva of elderly people requiring nursing care, respectively. the levels of inflammatory cytokines, interleukin (il)-6, and il-8 in ndusd-1 co-c ...201324077721
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