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in vitro evaluation of the acquisition of resistance, antifungal activity and synergism of brazilian red propolis with antifungal drugs on candida spp.to evaluate the ability of candida parapsilosis and candida glabrata to develop phenotypic resistance to a benzophenone enriched fraction obtained from brazilian red propolis (bzp-brp) as compared to fluconazole (flc). to investigate possible synergy between bzp-brp and flc and anidulafungin (and).201525565139
emergence of multiple resistance profiles involving azoles, echinocandins and amphotericin b in candida glabrata isolates from a neutropenia patient with prolonged fungaemia. 201525550394
candida glabrata esophagitis: are we seeing the emergence of a new azole-resistant pathogen?background. candida glabrata (c. glabrata) has become a recognized pathogen in fungal esophagitis. a proportion of these isolates are azole-resistant which may have treatment implications. variability in the prevalence of this organism exists in the limited data available. objective. to determine the incidence of c. glabrata esophagitis in a north american hospital setting and to highlight factors that may predispose patients to this condition. methods. patient charts were collected from january ...201425544843
contribution of (1,3)-beta-d-glucan to diagnosis of invasive candidiasis after liver transplantation.invasive candidiasis (ic) causes high morbidity and mortality rates after liver transplantation, in part due to delayed diagnosis. the fungal cell wall component (1,3)-beta-d-glucan (bg) could be an early biomarker of ic. this preliminary prospective study was designed to evaluate the contribution of bg measurements to the diagnosis of ic after liver transplantation. all consecutive patients who underwent liver transplantation at henri mondor hospital in france between january and june 2013 were ...201525520448
gastric trichobezoar associated with perforated peptic ulcer and candida glabrata infection.bezoars are accumulations of human or plant fiber located in the gastrointestinal tract of both humans and animals. patients remain asymptomatic for several years, and the symptoms develop as these accumulations increase in size to the point of obstruction or perforation. we report the case of a 21-year-old patient at 10 d postpartum, who presented with acute abdomen associated with sepsis. given the urgency of the clinical picture, at no point was the presence of a giant bezoar at gastric level ...201425516871
candida glabrata sepsis associated with chorioamnionitis in an ivf twin pregnancy: should we deliver?we report a case of in vitro fertilization (ivf)-acquired candida glabrata chorioamnionitis successfully treated through systemic maternal antifungal treatment prior to delivery. to the best of our knowledge, this is the first case of its kind in the literature. c. glabrata chorioamnionitis in pregnancy is rare, but the current literature suggests a very high fetal fatality in such cases. it is known to have an association with cervical stitch, amniocentesis, chorionic villous sampling, and assi ...201525510957
the cdc13-stn1-ten1 complex stimulates pol α activity by promoting rna priming and primase-to-polymerase switch.emerging evidence suggests that cdc13-stn1-ten1 (cst), an rpa-like ssdna-binding complex, may regulate primase-pol α (pp) activity at telomeres constitutively, and at other genomic locations under conditions of replication stress. here we examine the mechanisms of pp stimulation by cst using purified complexes derived from candida glabrata. while cst does not enhance isolated dna polymerase activity, it substantially augments both primase activity and primase-to-polymerase switching. cst also si ...201425503194
pretreatment of chemically-synthesized aβ42 affects its biological activity in yeast.the tendency of amyloid β (aβ42) peptide to misfold and aggregate into insoluble amyloid fibrils in alzheimer's disease (ad) has been well documented. accumulation of aβ42 fibrils has been correlated with abnormal apoptosis and unscheduled cell division which can also trigger the death of neuronal cells, while oligomers can also exhibit similar activities. while investigations using chemically-synthesized aβ42 peptide have become common practice, there appear to be differences in outcomes from d ...201425495906
the superoxide dismutases of candida glabrata protect against oxidative damage and are required for lysine biosynthesis, dna integrity and chronological life survival.the fungal pathogen candida glabrata has a well-defined oxidative stress response, is extremely resistant to oxidative stress and can survive inside phagocytic cells. in order to further our understanding of the oxidative stress response in c. glabrata, we characterized the superoxide dismutases (sods) cu,znsod (sod1) and mnsod (sod2). we found that sod1 is the major contributor to total sod activity and is present in cytoplasm, whereas sod2 is a mitochondrial protein. both sods played a central ...201525479837
compartmentalizing metabolic pathway in candida glabrata for acetoin production.acetoin, a valuable compound, has high potential as a biochemical building block. in this study, subcellular metabolic engineering was applied to engineer the mitochondrion of candida glabrata for acetoin production. with the aid of mitochondrial targeting sequences, a heterologous acetoin pathway was targeted into the mitochondria to increase the enzyme concentrations and level of intermediate, followed by coupling with the mitochondrial pyruvate carrier (mpc) to increase the availability of mi ...201525479455
antifungal susceptibilities of candida glabrata species complex, candida krusei, candida parapsilosis species complex and candida tropicalis causing invasive candidiasis in china: 3 year national surveillance.to define the antifungal susceptibility patterns of the most common non-albicans candida spp. in china.201525473027
the mannoprotein tir3 (cagl0c03872g) is required for sterol uptake in candida glabrata.sterol uptake in the pathogenic fungus, candida glabrata, occurs via the sterol transporter, cgaus1p. azole inhibition of sterol biosynthesis can under certain circumstances be reversed by adding exogenously sterol. here we demonstrate that the cgtir3 (cagl0c03872g) gene product is also required for sterol uptake, since cgtir3δ strains fail to take up sterol both aerobically and under hypoxic conditions. western analysis using an ha-tagged tir3 strain showed that cgtir3p localizes to the cell wa ...201525463012
candida glabrata meningitis and endocarditis: a late severe complication of candidemia.we report an unusual case of candida glabrata meningitis and endocarditis in a young caucasian woman with a prosthetic aortic valve and suffering from a dissecting thoraco-abdominal aortic aneurysm. c. glabrata was isolated from culture of the cerebrospinal fluid. candida infection of the central nervous system is an uncommon manifestation of disseminated infection due to candida species. our case report also highlights the intrinsic resistance of c. glabrata to azoles.201425449253
comparative effects of hypoxia and hypoxia mimetic cobalt chloride on in vitro adhesion, biofilm formation and susceptibility to amphotericin b of candida glabrata.candida glabrata has emerged as potent pathogen in nosocomial infections. the objective of this study is to investigate the effects of hypoxia (an important host factor) and hypoxia mimetic cobalt chloride upon growth, in vitro adhesion, biofilm formation and susceptibility to amphotericin b of candida glabrata.201425442919
failed reverse total shoulder arthroplasty caused by recurrent candida glabrata infection with prior serratia marcescens coinfection.this report describes a 58-year-old insulin-dependent diabetic male patient who initially sustained a proximal humerus fracture from a fall. the fracture fixation failed and then was converted to a humeral hemiarthroplasty, which became infected with candida glabrata and serratia marcescens. after these infections were believed to be cured with antibacterial and antifungal treatments and two-stage irrigation and debridement, he underwent conversion to a reverse total shoulder arthroplasty. unfor ...201425431708
chemical composition profiling and antifungal activity of the essential oil and plant extracts of mesembryanthemum edule (l.) bolus leaves.essential oil from mesembryanthemum edule leaves have been used by the eastern cape traditional healers for the treatment of respiratory tract infections, tuberculosis, dysentery, diabetic mellitus, laryngitis and vaginal infections. the investigation of bioactive compounds in the essential oil of this plant could help to verify the efficacy of the plant in the management or treatment of these illnesses.201425392576
weekly use of fluconazole as prophylaxis in haematological patients at risk for invasive candidiasis.the goal was to determine whether one medical centres' unique antifungal prophylactic regimen for patients at high risk for invasive candidiasis because of their haematological malignancies, haematopoietic stem cell transplants, or high-dose chemotherapy might lead ultimately to a higher incidence of infection, to increasing fluconazole resistance, or to a shift in the predominant strain of candida in invasive fungal episodes.201425384689
resistance reversal induced by a combination of fluconazole and tacrolimus (fk506) in candida glabrata.there is an increasing concern about candida glabrata due to its high isolation frequency in candidiasis recently and notorious drug resistance to fluconazole. drug combination is one effective approach to counteract drug resistance. this study aimed to test whether a combination of fluconazole and tacrolimus (fk506) had a synergistic effect on c. glabrata, and to seek the potential mechanisms underlying the synergistic effects. in vitro effects of fluconazole and fk506 against c. glabrata with ...201525355935
drug-resistant candida glabrata infection in cancer patients.cancer patients are at risk for candidemia, and increasing candida spp. resistance poses an emerging threat. we determined rates of antifungal drug resistance, identified factors associated with resistance, and investigated the correlation between resistance and all-cause mortality rates among cancer patients with ≥1 c. glabrata-positive blood culture at md anderson cancer center, houston, texas, usa, during march 2005-september 2013. of 146 isolates, 30 (20.5%) were resistant to fluconazole, 15 ...201425340258
serum albumin promotes atp-binding cassette transporter-dependent sterol uptake in yeast.sterol uptake in fungi is a multistep process that involves interaction between external sterols and the cell wall, incorporation of sterol molecules into the plasma membrane, and subsequent integration into intracellular membranes for turnover. atp-binding cassette (abc) transporters have been implicated in sterol uptake, but key features of their activity remain to be elucidated. here, we apply fluorescent cholesterol (nbd-cholesterol) to monitor sterol uptake under anaerobic and aerobic condi ...201425331273
changes in genotype and fluconazole susceptibility of isolates from patients with candida glabrata in tunisia.candida glabrata has emerged as an opportunistic pathogen of considerable importance in invasive and superficial infections.201425285365
novel intein-containing dna specific primers for rapid identification of candida glabrata using real-time pcr assays.candida glabrata is an opportunistic human pathogen known to cause systemic and vaginal candidiasis. rapid detection of candida glabrata is indispensable for appropriate selection of antifungal drugs for chemotherapy. the study describes a unique intein-containing dna fragment for specific detection of c. glabrata. the designed oligonucleotides detected c. glabrata (ct mean: 24.75 ± 1.1 and tm: 70.08 ± 0.23°c) in real-time pcr assays. the fluorescent signals were negative when the primers were t ...201425282343
microbiology, infection control and infection related outcome in pediatric patients in an oncology center in eastern india: experience from tata medical center, kolkata.infection is a major determinant in the outcome of patients with cancer.201626842142
an essential role for phosphatidylinositol 3-kinase in the inhibition of phagosomal maturation, intracellular survival and virulence in candida glabrata.the yeast class iii phosphoinositide 3-kinase (pi3k) that catalyses production of the lipid signalling molecule, phosphatidylinositol-3-phosphate, is primarily implicated in vesicle-mediated transport and autophagy. in this study, we identified, through a genetic screen, the candida glabrata cgvps15 gene, an orthologue of the saccharomyces cerevisiae pi3k regulatory subunit-encoding open reading frame (orf) to be required for impairment of phagosomal maturation in human macrophages. we also disr ...201525223215
osteomyelitis caused by candida glabrata in the distal phalanx.osteomyelitis caused by candida glabrata is rare and its optimal treatment is unknown. here we report a case of osteomyelitis caused by c. glabrata in the distal phalanx in a 54-year-old woman. despite partial resection of the nail and administering a 1-month course of antibiotics for paronychia, the local swelling remained and an osteolytic lesion was found. c. glabrata osteomyelitis of the distal phalanx was later diagnosed after curettage. thereafter, the patient was treated with antifungal a ...201425215255
metabolism in fungal pathogenesis.fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. we focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host-fungus interactions during infection. we highlight several emerging trends based on the available data. first, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates fungal pathogenicity. second, the contrasting evolutionary pressures exerted on facultative versus ob ...201425190251
[the use of caspofungin in extremely low birth weight preterm infants based on clinical trials and reports considering the own experience (case report)].in recent years, despite of significant progress in the treatment of premature infants with extremely low body weight, still a significant problem remains severe, treatment-resistant generalized infections among which the percentage of fungal infections is increasing. the invasive candidiasis, especially caused by non-albicans species of candida, are of particular importance. in the case of resistance on fluconazole and amphotericin b the use of echinocandin drug may be a useful choice. this pap ...201425182262
contribution of the slt2-regulated transcription factors to echinocandin tolerance in candida glabrata.echinocandin-class antifungals, including micafungin, are considered as the first-line treatment for candida glabrata infections. however, recent epidemiological surveys have revealed an increasing number of c. glabrata isolates exhibiting decreased echinocandin susceptibilities. the slt2 mitogen-activated protein kinase pathway is important for maintenance of cell wall integrity in fungi. rlm1 and swi4-swi6 cell cycle box binding factor (sbf) are transcription factors downstream of slt2. while ...201425175946
environmental azole fungicide, prochloraz, can induce cross-resistance to medical triazoles in candida glabrata.acquisition of azole resistance by clinically relevant yeasts in nature may result in a significant, yet undetermined, impact in human health. the main goal of this study was to assess the development of cross-resistance between agricultural and clinical azoles by candida spp. an in vitro induction assay was performed, for a period of 90 days, with prochloraz (pcz) - an agricultural antifungal. afterward, the induced molecular resistance mechanisms were unveiled. mic value of pcz increased signi ...201425132632
direct visualization of fungal infection in brains from patients with alzheimer's disease.recently, we have reported the presence of fungal infections in patients with alzheimer's disease (ad). accordingly, fungal proteins and dna were found in brain samples, demonstrating the existence of infection in the central nervous system. in the present work, we raised antibodies to specific fungal species and performed immunohistochemistry to directly visualize fungal components inside neurons from ad patients. mice infected with candida glabrata were initially used to assess whether yeast c ...201525125470
candida glabrata endophthalmitis transmitted from graft to host after descemet stripping automated endothelial keratoplasty. 201425124791
evaluation of blood culture media for the detection of fungi.the aim of this study was to compare the utility of bactec™ mycosis-ic/f (mycosis), bactec™ plus aerobic/f (aerobic), and bactec™ plus anaerobic/f (anaerobic) media in the detection of fungi from simulated (obtained by the inoculation of tested media first with sterile sheep's blood and subsequently with one of 60 clinical yeast isolates) and clinical blood samples, taken during routine diagnostic examination in two hospitals. all tested strains grew on mycosis as well as aerobic bottles, and th ...201525098681
isolation, selection and evaluation of yeasts for use in fermentation of coffee beans by the wet process.during wet processing of coffee, the ripe cherries are pulped, then fermented and dried. this study reports an experimental approach for target identification and selection of indigenous coffee yeasts and their potential use as starter cultures during the fermentation step of wet processing. a total of 144 yeast isolates originating from spontaneously fermenting coffee beans were identified by molecular approaches and screened for their capacity to grow under coffee-associated stress conditions. ...201425087206
longer incubation times for yeast fungemia: importance for presumptive treatment.isolation rates of candida glabrata at ≤2 days were 8.9% and 34.8% at >2 days; for cryptococcus neoformans, they were 0.9% and 8.6%, respectively (1741 fungemia analyzed). an incubation time >2 days supports candins as presumptive treatment for c. glabrata, keeping in mind the risk of cryptococcus fungemia.201425085022
prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period.to describe temporal trends in the epidemiology, clinical management and outcome of candidemia in intensive care unit (icu) patients.201425082359
pivotal role for a tail subunit of the rna polymerase ii mediator complex cgmed2 in azole tolerance and adherence in candida glabrata.antifungal therapy failure can be associated with increased resistance to the employed antifungal agents. candida glabrata, the second most common cause of invasive candidiasis, is intrinsically less susceptible to the azole class of antifungals and accounts for 15% of all candida bloodstream infections. here, we show that c. glabrata med2 (cgmed2), which codes for a tail subunit of the rna polymerase ii mediator complex, is required for resistance to azole antifungal drugs in c. glabrata. an in ...201425070095
fumaric acid production by torulopsis glabrata: engineering the urea cycle and the purine nucleotide cycle.a multi-vitamin auxotrophic torulopsis glabrata strain, a pyruvate producer, was further engineered to produce fumaric acid. using the genome-scale metabolic model inx804 of t. glabrata, four fumaric acid biosynthetic pathways, involving the four cytosolic enzymes, argininosuccinate lyase (asl), adenylosuccinate lyase (adsl), fumarylacetoacetase (faa), and fumarase (fum1), were found. athough single overexpression of each of the four enzymes in the cytosol improved fumaric acid production, the h ...201525060134
time-kill assay and etest evaluation for synergy with polymyxin b and fluconazole against candida glabrata.fluconazole-resistant candida glabrata is an emerging pathogen that causes fungemia. polymyxin b, a last-resort antibiotic used to treat multidrug-resistant gram-negative bacterial infections, has been found to possess in vitro fungicidal activity and showed synergy with fluconazole against a single strain of c. glabrata. since both agents may be used simultaneously in intensive care unit (icu) patients, this study was performed to test for possible synergy of this combination against 35 c. glab ...201425049251
engineering the carbohydrate-binding site of epa1p from candida glabrata: generation of adhesin mutants with different carbohydrate specificity.the n-terminal domain of the epa1p adhesin from candida glabrata (n-epa1p) is a calcium-dependent lectin, which confers the opportunistic yeast the ability to adhere to human epithelial cells. this lectin domain is able to interact with galactosides and, more precisely, with glycan molecules containing the galβ-1,3-galnac disaccharide, also known as the t-antigen. based on the crystallographic structure of the n-epa1p domain and the role of the variable loop cbl2 in glycan binding, saturation mu ...201425049238
[fructose transporter in yeasts].study of hexoses transporter started with discovery of galactose permease in saccharomyces cerevisiae. glucose, fructose and mannose assimilation is assumed by numerous proteins encoded by different genes. to date over 20 hexoses transporters, belonging to sugar porter family and to major facilitator superfamily, were known. genome sequence analysis of candida glabrata, kluyveromyces lactis, yarrowia lipolytica, s. cerevisaie and debaryomyces hansenii reveled potential presence of 17-48 sugar po ...201425033548
[case of candidemia with candida glabrata with confirmation of the acquisition of micafungin sensitivity due to new mutation of fks gene mutation]. 201425033496
occurrence and characterization of candida nivariensis from a culture collection of candida glabrata clinical isolates in malaysia.candida nivariensis and c. bracarensis have been recently identified as emerging yeast pathogens which are phenotypically indistinguishable from c. glabrata. however, there is little data on the prevalence and antifungal susceptibilities of these species.201425022264
[evaluation of the vitek 2 system (ast-yso1 cards) for antifungal susceptibility testing against different candida species].the aim of this investigation was to evaluate the results of antifungal susceptibility for various candida species using the vitek 2 semi-automated system (ast-yso1 cards, biomérieux), and to compare them with those obtained by the clsi (clinical and laboratory standards institute) broth microdilution reference method (document m27-a3,2008). the essential agreement (ea) was > 90%, except for candida glabrata against voriconazole (vcz); and for candida krusei against fluconazole (fcz). the overal ...201425011594
a systematic analysis reveals an essential role for high-affinity iron uptake system, haemolysin and cfem domain-containing protein in iron homoeostasis and virulence in candida glabrata.iron is an essential nutrient for all living organisms and human pathogens employ a battery of factors to scavenge iron from the high-affinity iron-binding host proteins. in the present study, we have elucidated, via a candidate gene approach, major iron acquisition and homoeostatic mechanisms operational in an opportunistic human fungal pathogen candida glabrata. phenotypic, biochemical and molecular analysis of a set of 13 c. glabrata strains, deleted for proteins potentially implicated in iro ...201424987864
yeasts vectored by migratory birds collected in the mediterranean island of ustica and description of phaffomyces usticensis f.a. sp. nov., a new species related to the cactus ecoclade.nine yeast species belonging to genera candida, cryptococcus, phaffomyces, rhodotorula and wickerhamomyces, and one species of aureobasidium genus were isolated from the cloaca of migratory birds. candida glabrata and c. inconspicua were the species most frequently isolated and wickerhamomyces sylviae, which has recently been described as a new species isolated from bird cloaca, was again found. the majority of isolates showed the ability to grow up to 40 °c and/or at ph 3.0, two environmental c ...201424981278
[a case of micafungin-hyposensitive candida glabrata due to fks2 gene mutation].candida glabrata was continuously isolated in cultured urine samples from a subject with thrombotic thrombocytopenic purpura. yeast-like fungal phagocytosis found in gram staining led to agents being tested for antifungal susceptibility, revealing hyposensitivity to micafungin (mcfg) of mic < 2 mg/ml. mcfg administered for 10 days failed to cure c. glabrata infection. to clarify why hyposensitivity occurred, we analyzed the fks gene sequence using the pcr, finding a deficit of 3 bases coding phe ...201424979950
systematic phenotyping of a large-scale candida glabrata deletion collection reveals novel antifungal tolerance genes.the opportunistic fungal pathogen candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. the inherent tolerance of c. glabrata to azole drugs makes this pathogen a serious clinical threat. to identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale c. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, al ...201424945925
evaluation of possibilities in identification and susceptibility testing for candida glabrata clinical isolates with the integral system yeast plus (isyp).the aim of this study was to evaluate possibilities of correct identification and susceptibility testing of c. glabrata clinical isolates with integral system yeast plus (isyp). for species identification, as the reference method, api candida test and species-specific pcr reactions were used. the potential of antifungal susceptibility testing by the isyp test was compared with the sensititre yeast one. whilst the reference methods confirmed that the received population (n = 65 isolates) represen ...201424939684
a case of candida glabrata severe urinary sepsis successfully treated with micafungin.candida glabrata is frequently resistant to fluconazole, and in advanced renal failure the safe use of this and other recommended drugs is limited. we report a case of a 56 years-old diabetic woman with renal failure and severe urinary sepsis from c. glabrata successfully treated with micafungin.201424936401
fluconazole affects the alkali-metal-cation homeostasis and susceptibility to cationic toxic compounds of candida glabrata.candida glabrata is a salt-tolerant and fluconazole (flc)-resistant yeast species. here, we analyse the contribution of plasma-membrane alkali-metal-cation exporters, a cation/proton antiporter and a cation atpase to cation homeostasis and the maintenance of membrane potential (δψ). using a series of single and double mutants lacking cnh1 and/or ena1 genes we show that the inability to export potassium and toxic alkali-metal cations leads to a slight hyperpolarization of the plasma membrane of c ...201424913686
in vitro evaluation of the enzymatic activity profile of non-albicans candida species isolated from patients with oral candidiasis with or without diabetes.to evaluate the expression of phospholipase (pl) and secreted aspartyl proteinase (sap) by candida glabrata and c tropicalis obtained from the denture biofilms of healthy participants (16 isolates), patients with oral candidiasis with diabetes (10 isolates), and patients with oral candidiasis without diabetes (25 isolates).201424908598
time to positivity and detection of growth in anaerobic blood culture vials predict the presence of candida glabrata in candidemia: a two-center european cohort study.this study shows the accuracy of exclusive or earlier growth in anaerobic vials to predict candida glabrata in a large series of candidemic patients from two european hospitals using the bactec 9240 system. alternatively, c. glabrata can be predicted by a time to positivity cutoff value, which should be determined for each setting.201424899027
evaluation of multiplex pcr in first episodes of febrile neutropenia as a tool to improve early yeast diagnosis in leukemic/preleukemic patients.in febrile neutropenic onco-hematological patients, delayed microbiological diagnosis leads to an increase in morbidity and mortality. identification of the microorganism changes antibiotic therapy in more than half of cases; however, in only 20-30 % of such cases pathogen isolation is achieved. this study evaluates the frequency of fungus infection and its etiology in onco-hematological patients with febrile neutropenia utilizing blood cultures and non-commercial multiplex polymerase chain reac ...201424897963
role of fks mutations in candida glabrata: mic values, echinocandin resistance, and multidrug resistance.candida glabrata is the second leading cause of candidemia in u.s. hospitals. current guidelines suggest that an echinocandin be used as the primary therapy for the treatment of c. glabrata disease due to the high rate of resistance to fluconazole. recent case reports indicate that c. glabrata resistance to echinocandins may be increasing. we performed susceptibility testing on 1,380 isolates of c. glabrata collected between 2008 and 2013 from four u.s. cities, atlanta, baltimore, knoxville, and ...201424890592
fks mutant candida glabrata: risk factors and outcomes in patients with candidemia.echinocandins are recommended for candia glabrata candidemia. mutations in the fks1 and fks2 genes are associated with echinocandin resistance. few studies have assessed risk factors for fks mutant isolates and outcomes in patients receiving micafungin treatment.201424879785
breakthrough invasive fungal disease in patients receiving posaconazole primary prophylaxis: a 4-year study.posaconazole (psc) is currently recommended as primary prophylaxis in neutropenic patients with acute myeloid leukaemia (aml) and in allogenic haematopoietic stem cell transplantation (ahsct) recipients with graft-versus-host disease (gvhd). studies focusing on breakthrough invasive fungal disease (ifd) upon psc prophylaxis show disparate results. in order to evaluate the incidence of ifd in patients on psc prophylaxis and identify ifd risk factors, we carried out a retrospective study of all co ...201424861577
microbiocidal effects of various taurolidine containing catheter lock solutions.we have recently shown that a catheter lock solution containing taurolidine dramatically decreases catheter-related bloodstream infections (crbsi) in patients on home parenteral nutrition (hpn) when compared to heparin. since several taurolidine formulations are commercially available, some of which also contain citrate or heparin, we were interested in the effect of these different locks on growth and biofilm formation of fungal, gram-negative and gram-positive pathogens that are known to imped ...201524861410
in vitro antifungal activities of leaf extracts of lippia alba (verbenaceae) against clinically important yeast species.there are few studies reporting the antifungal activities of lippia alba extracts.201424861304
milbemycin a4 oxime as a probe of azole transport in candida glabrata.azole resistance in candida glabrata, a pathogenic yeast, has prompted studies of compounds that have therapeutic potential by reversing azole resistance. milbemycin a4 oxime blocked azole efflux and enhanced azole susceptibility fourfold in 28 clinical isolates of c. glabrata. specificity of the milbemycin a4 oxime effect depended on the drug transporter and the substrate being effluxed. the major effect of milbemycin a4 oxime was inhibition of azole and rhodamine 6g efflux by the atp-binding c ...201424838041
polymerase chain reaction melting profiles of candida glabrata clinical isolates in solid organ transplant recipients in comparison to the other group of surgical patients.the aim of the retrospective study were to estimate the prevalence of candida glabrata in liver and kidney transplant recipients compared to patients with short bowel syndrome receiving chronic total parenteral nutrition and relevance of the polymerase chain reaction melting profile (pcr mp) method for candida glabrata strains differentiation. c. glabrata clinical strains isolated from patients were identified by using standard mycological procedures. the analysis of genetic relatedness of the i ...201424836833
set of classical pcrs for detection of mutations in candida glabrata fks genes linked with echinocandin resistance.clinical echinocandin resistance among candida glabrata strains is increasing, especially in the united states. antifungal susceptibility testing is considered mandatory to guide therapeutic decisions. however, these methodologies are not routinely performed in the hospital setting due to their complexity and the time needed to obtain reliable results. echinocandin failure in c. glabrata is linked exclusively to fks1p and fks2p amino acid substitutions, and detection of such substitutions would ...201424829248
diagnostic usefulness of differential time to positivity for catheter-related candidemia.a differential time to positivity (dtp) of ≥ 120 min is useful for diagnosing catheter-related bacteremia, but data on diagnosing catheter-related candidemia (crc) in this way are limited. we wished to evaluate the usefulness of the dtp for diagnosing crc. all adult patients who had the same candida species isolated from blood cultures drawn simultaneously from a central venous catheter (cvc) and a peripheral vein were included at a tertiary care hospital over an 18-month period. a total of 105 ...201424829236
candida glabrata intra-abdominal candidiasis is characterized by persistence within the peritoneal cavity and abscesses.the pathogenesis of candida glabrata infections is poorly understood. we studied the pathogenesis of intra-abdominal candidiasis (iac) in mice that were infected intraperitoneally with c. glabrata and sterile feces. c. glabrata bg2 (5 × 10(8) cfu) caused a 100% mortality rate. sublethal inocula of bg2 (1 × 10(8) or 1 × 10(7) cfu) caused peritonitis that progressed to abscesses. three clinical c. glabrata strains (5 × 10(8) cfu) caused 80 to 100% mortality rates, while a fourth (strain 346) cause ...201424799629
breakthrough invasive candida glabrata in patients on micafungin: a novel fks gene conversion correlated with sequential elevation of mic.candida glabrata strains sequentially isolated from blood developed resistance to micafungin (mics from <0.015 to 4 μg/ml). a novel mutation identified in micafungin-resistant strains at bp 262 of fks2 (containing a deletion of f659 [f659del]) was inserted into the homologous region in fks1.201424789192
recurrent arthritis by candida glabrata, a diagnostic and therapeutic challenge.infectious arthritis due to candida glabrata is very rare. a 40-year-old iranian man had developed a painful swelling on the left knee since a year ago. a surgery (meniscectomy) was performed on his knee. however, in follow-up visit after 2 months, the patient's condition was deteriorated. direct examination of synovial fluid with gram and hematoxylin-eosin stains were negative for any bacterial or fungal infection or crystal elements; however, inoculation into bactec™ mycosis ic/f and plus aero ...201424752453
in vitro antifungal susceptibility of candida glabrata to caspofungin and the presence of fks mutations correlate with treatment response in an immunocompromised murine model of invasive infection.it has been argued that the in vitro activity of caspofungin (csp) is not a good predictor of the outcome of echinocandin treatment in vivo. we evaluated the in vitro activity of csp and the presence of fks mutations in the hot spot 1 (hs1) region of the fks1 and fks2 genes in 17 candida glabrata strains with a wide range of mics. the efficacy of csp against systemic infections from each of the 17 strains was evaluated in a murine model. no hs1 mutations were found in the eight strains showing m ...201424733474
histidine degradation via an aminotransferase increases the nutritional flexibility of candida glabrata.the ability to acquire nutrients during infections is an important attribute in microbial pathogenesis. amino acids are a valuable source of nitrogen if they can be degraded by the infecting organism. in this work, we analyzed histidine utilization in the fungal pathogen of humans candida glabrata. hemiascomycete fungi, like c. glabrata or saccharomyces cerevisiae, possess no gene coding for a histidine ammonia-lyase, which catalyzes the first step of a major histidine degradation pathway in mos ...201424728193
enhancement of acetoin production in candida glabrata by in silico-aided metabolic engineering.acetoin is a promising chemical compound that can potentially serve as a high value-added platform for a broad range of applications. many industrial biotechnological processes are moving towards the use of yeast as a platform. the multi-auxotrophic yeast, candida glabrata, can accumulate a large amount of pyruvate, but produces only trace amounts of acetoin. here, we attempted to engineer c. glabrata to redirect the carbon flux of pyruvate to increase acetoin production.201424725668
genome-wide survey of transcriptional initiation in the pathogenic fungus, candida glabrata.dna sequencing of the 5'-flanking region of the transcriptome effectively identifies transcription initiation sites and also aids in identifying unknown genes. this study describes a comprehensive polling of transcription start sites and an analysis of full-length complementary dnas derived from the genome of the pathogenic fungus candida glabrata. a comparison of the sequence reads derived from a cdna library prepared from cells grown under different culture conditions against the reference gen ...201424725256
isolation of cholesterol-dependent, multidrug-resistant candida glabrata strains from blood cultures of a candidemia patient in kuwait.candida glabrata has emerged as an important human pathogen associated with systemic and mucosal infections. here, we describe isolation of two cholesterol-dependent candida glabrata strains from a candidemia patient which failed to grow on the media devoid of a cholesterol source.201424712485
fatal case of candidemia due to candida glabrata. 201424696185
candida glabrata and pre-term premature rupture of membrane complicating in vitro pregnancy: case report and confirmation of mother to neonate transmission.we report a case of candida glabrata infection in an in vitro fertilization-assisted pregnancy complicated by pre-term pre-labor rupture of the membranes. we found c. glabrata in gastric fluid, amniotic fluid and maternal vaginal swab. neonatal and maternal isolates showed indistinguishable molecular patterns analyzed by fingerprint dna multilocus.201424691825
severe systemic candidiasis following immunomodulation therapy in in vitro fertilisation-embryo transfer (ivf-et).a 41-year-old nulliparous woman, with a medical history of unexplained infertility and multiple in vitro fertilisation (ivf) cycles with immunosuppressive therapy, was admitted to our tertiary obstetrics unit with sepsis at 18 weeks of pregnancy with dichorionic diamniotic twins. candida glabrata was grown from her blood cultures, then subsequently from the liquor and placentae. she was treated with intravenous ambisome (amphotericin), but unfortunately, the infection resulted in the rupture of ...201424686802
phenotypic analysis of a family of transcriptional regulators, the zinc cluster proteins, in the human fungal pathogen candida glabrata.candida glabrata is the second most important human fungal pathogen. despite its formal name, c. glabrata is in fact more closely related to the nonpathogenic budding yeast saccharomyces cerevisiae. however, less is known about the biology of this pathogen. zinc cluster proteins form a large family of transcriptional regulators involved in the regulation of numerous processes such as the control of the metabolism of sugars, amino acids, fatty acids, as well as drug resistance. the c. glabrata ge ...201424657903
the impact of new epidemiological cutoff values on candida glabrata resistance rates and concordance between testing methods.interpretive criteria for candida susceptibility testing were recently revised with the establishment of species-specific epidemiological cutoff values (ecv). to assess the effect of modified cutoff values on candida glabrata resistance rates and agreement between testing methods, we tested the susceptibility of 598 clinical isolates to fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, and amphotericin b using clsi m27-a3 and e-test methods. the caspofungin mics clustered above ...201424657169
effects of fluconazole on candida glabrata biofilms and its relationship with abc transporter gene expression.candida glabrata has emerged as the second most prevalent fungal pathogen and its ability to form biofilms has been considered one of the most important virulence factors, since biofilms present a high tolerance to antifungal agents used in fungal infection treatment. the mechanisms of biofilm tolerance to antifungal agents remain poorly understood. thus, the aim of this study was to evaluate the effects of fluconazole (flu) on the formation and control of c. glabrata biofilms and its relation w ...201424645630
purification of g1 daughter cells from different saccharomycetes species through an optimized centrifugal elutriation procedure.centrifugal elutriation discriminates cells according to their sedimentation coefficients, generating homogeneous samples well suited for genomic comparative approaches. it can, for instance, isolate g1 daughter cells from a saccharomyces cerevisiae unsynchronized population, alleviating ageing and cell-cycle biases when conducting genome-wide/single-cell studies. the present report describes a straightforward and robust procedure to determine whether a cell population of virtually any yeast spe ...201424604765
isolation of antifungal compound from paeonia suffruticosa and its antifungal mechanism.to isolate antifungal compound from paeonia suffruticosa, and to find the antifungal mechanisms by observing the ultrastructural modifications of yeasts in growth phase produced by 1,2,3,4,6-penta-o-galloyl-beta-d-glucose (pgg).201524577809
candida glabrata drug:h+ antiporter cgtpo3 (orf cagl0i10384g): role in azole drug resistance and polyamine homeostasis.the ability of opportunistic pathogenic candida species to persist and invade specific niches in the human host depends on their resistance to natural growth inhibitors and antifungal therapy. this work describes the role of the candida glabrata drug:h(+) antiporter cgtpo3 (orf cagl0i10384g) in this context.201424576949
candida glabrata vertebral osteomyelitis in an immunosuppressed patient. 201424576284
two non-exclusive strategies employed to protect torulopsis glabrata against hyperosmotic stress.several recent reports described an apoptosis-like programmed cell death (pcd) process in yeast in response to different environmental challenges. in this study, hyperosmotic stress caused by high nacl concentration in culture medium induced cell death in the haploid yeast torulopsis glabrata. propidium iodide (pi) and pi/rhodamine-123 (rh123) dual staining with flow cytometry showed that high salinity decreased intact cells by 16.5 %, increased necrotic cells by nearly twofold, and altered ferm ...201424562390
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
assessment of caspofungin susceptibility of candida glabrata by the etest®, clsi, and eucast methods, and detection of fks1 and fks2 mutations.candida glabrata has emerged as a major pathogen in invasive candidiasis in recent years. currently, guidelines for invasive candidiasis treatment recommend fluconazole or an echinocandin as the first-line therapy. nevertheless, the resistance of candida glabrata to echinocandin is an emerging problem and has been partly associated with mutations in the fks1 and fks2 genes. the etest® is an appropriate method for determining antifungal susceptibility in emergency routine diagnosis. in this work, ...201424522619
recurrent catheter related bloodstream infections by candida glabrata: successful treatment with taurolidine. 201424485770
[bilateral endogenous ophthalmitis due to candida glabrata after complicated bariatric surgery].a 43 year-old female presented with decreased visual acuity in the right eye. «snowball-like» retinal lesions were found in both eyes on examination. due to a lack of improvement with intravitreal antifungal empirical treatment, vitreous culture was performed and candida glabrata was isolated. the patient then received intravitreal amphotericin b, as well as systemic treatment with caspofungin and amphotericin b lipid complex.201424485524
breakthrough candidemia due to multidrug-resistant candida glabrata during prophylaxis with a low dose of micafungin.we identified a case of breakthrough candidemia in a 25-year-old patient receiving micafungin prophylaxis (50 mg/day). five candida glabrata isolates were obtained from blood cultures and were classified as multidrug-resistant isolates, since all of them exhibited high mics for echinocandin and azole drugs. a mutation (s663f) in hot spot 1 of the fks2 gene was found in all five isolates. this mutation yielded a 1,3-β-d-glucan synthase enzyme with highly reduced sensitivities to echinocandin drug ...201424468776
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
candida glabrata infection following total hip arthroplasty: a case report.candida glabrata infection following total hip arthroplasty is rare and, due to the insufficiency of standardized clinical and evidence-based guidelines, there is no appropriate therapeutic schedule. the present study reports the case of a 44-year-old patient with candida glabrata infection following a total hip arthroplasty. the patient was successfully treated by administration of intravenous and oral voriconazole without removal of the prosthesis. this case illustrates the significance of pos ...201424396403
a simple and inexpensive device for biofilm analysis.the calgary biofilm device (cbd) has been described as a technology for the rapid and reproducible assay of biofilm susceptibilities to antibiotics. in this study a simple and inexpensive alternative to the cbd was developed from polypropylene (pp) microcentrifuge tubes and pipette tip boxes. the utility of the device was demonstrated using candida glabrata, a yeast that can develop antimicrobial-resistant biofilm communities. biofilms of c. glabrata were formed on the outside surface of microce ...201424389040
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
update on antifungal resistance in aspergillus and candida.antifungal resistance in candida and aspergillus may be either intrinsic or acquired and may be encountered in the antifungal drug exposed but also the antifungal drug-naïve patient. prior antifungal treatment confers a selection pressure and notoriously raises the awareness of possible resistance in patients failing therapy, thus calling for susceptibility testing. on the contrary, antifungal resistance in the drug-naïve patient is less expected and therefore more challenging. this is particula ...201424372701
engineering of carboligase activity reaction in candida glabrata for acetoin production.utilization of candida glabrata overproducing pyruvate is a promising strategy for high-level acetoin production. based on the known regulatory and metabolic information, acetaldehyde and thiamine were fed to identify the key nodes of carboligase activity reaction (car) pathway and provide a direction for engineering c. glabrata. accordingly, alcohol dehydrogenase, acetaldehyde dehydrogenase, pyruvate decarboxylase, and butanediol dehydrogenase were selected to be manipulated for strengthening t ...201424365210
immune evasion, stress resistance, and efficient nutrient acquisition are crucial for intracellular survival of candida glabrata within macrophages.candida glabrata is both a human fungal commensal and an opportunistic pathogen which can withstand activities of the immune system. for example, c. glabrata can survive phagocytosis and replicates within macrophages. however, the mechanisms underlying intracellular survival remain unclear. in this work, we used a functional genomic approach to identify c. glabrata determinants necessary for survival within human monocyte-derived macrophages by screening a set of 433 deletion mutants. we identif ...201424363366
development of a luminex-based multiplex assay for detection of mutations conferring resistance to echinocandins in candida glabrata.echinocandins are the recommended treatment for invasive candidiasis due to candida glabrata. resistance to echinocandins is known to be caused by nonsynonymous mutations in the hot spot-1 (hs1) regions of the fks1 and fks2 genes, which encode a subunit of the β-1,3-glucan synthase, the target of echinocandins. here, we describe the development of a microsphere-based assay using luminex magpix technology to identify mutations in the fks1 hs1 and fks2 hs1 domains, which confer in vitro echinocand ...201424353003
role of dectin-2 for host defense against systemic infection with candida glabrata.although candida glabrata is an important pathogenic candida species, relatively little is known about its innate immune recognition. here, we explore the potential role of dectin-2 for host defense against c. glabrata. dectin-2-deficient (dectin-2(-/-)) mice were found to be more susceptible to c. glabrata infections, showing a defective fungal clearance in kidneys but not in the liver. the increased susceptibility to infection was accompanied by lower production of t helper 1 (th1) and th17-de ...201424343653
gpi (glycosylphosphatidylinositol)-linked aspartyl proteases regulate vacuole homoeostasis in candida glabrata.a family of 11 gpi (glycosylphosphatidylinositol)-linked cell surface-associated aspartyl proteases (yapsins) in the human opportunistic fungal pathogen candida glabrata is required for cell wall remodelling, ph homoeostasis, survival in macrophages and virulence in a murine model of disseminated candidiasis. in the present paper, we report new roles for yapsins in c. glabrata physiology and implicate them for the first time in the regulation of vacuole homoeostasis. in the present study we show ...201424341558
er stress response mechanisms in the pathogenic yeast candida glabrata and their roles in virulence.the maintenance of endoplasmic reticulum (er) homeostasis is critical for numerous aspects of cell physiology. eukaryotic cells respond to the accumulation of misfolded proteins in the er (er stress) by activating the unfolded protein response (upr), an intracellular signaling pathway that adjusts the folding capacity of the er. recent studies of several pathogenic fungi have revealed that the upr is important for antifungal resistance and virulence; therefore, the pathway has attracted much att ...201424335436
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
cell density impacts on candida glabrata survival in hypo-osmotic stress.candida glabrata cells suspended in water are under hypo-osmotic stress and undergo cell death in 1-2 days, unless they are at a density of more than 10(5 ) cfu ml(-1) . the dying cells exhibit fitc-annexin v staining, indicative of programmed cell death (apoptosis). in a higher cell density, cells are protected and survive at least for 4 days. filtrates from cells at high density can protect those at lower density, indicating that cells release substances, amounting to c. 5 mg l(-1) of cell sus ...201424305439
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