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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
the secretory pathway: exploring yeast diversity.protein secretion is an essential process for living organisms. in eukaryotes, this encompasses numerous steps mediated by several hundred cellular proteins. the core functions of translocation through the endoplasmic reticulum membrane, primary glycosylation, folding and quality control, and vesicle-mediated secretion are similar from yeasts to higher eukaryotes. however, recent research has revealed significant functional differences between yeasts and mammalian cells, and even among diverse y ...201323480475
comparison of sterol import under aerobic and anaerobic conditions in three fungal species, candida albicans, candida glabrata, and saccharomyces cerevisiae.sterol import has been characterized under various conditions in three distinct fungal species, the model organism saccharomyces cerevisiae and two human fungal pathogens candida glabrata and candida albicans, employing cholesterol, the sterol of higher eukaryotes, as well as its fungal equivalent, ergosterol. import was confirmed by the detection of esterified cholesterol within the cells. comparing the three fungal species, we observe sterol import under three different conditions. first, as p ...201323475705
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
candida glabrata prosthetic hip infection.we present a case of a 60-year-old caucasian woman carrying a 2-year-old hip prosthesis infected by candida glabrata dose-dependent susceptible to fluconazole and voriconazole. resection arthroplasty was performed. six weeks of caspofungin plus liposomal amphotericin combination therapy achieved joint sterilization and allowed a successfully reimplantation arthroplasty. in addition we review 9 cases of c. glabrata prosthetic joint infection described to date in the literature.201223431513
in vitro anticandidal evaluation of novel highly functionalized bis cyclohexenone ethyl carboxylates.novel highly functionalized bis cyclohexenone ethyl carboxylates 7-12 were designed, synthesized and their structures were elucidated by their elemental analysis, ms, ft-ir, one-dimensional 1h, and 13c nmr spectroscopic data.201323426531
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
the new mutation l321f in candida albicans erg11 gene may be associated with fluconazole resistance.for many years fluconazole has been commonly used to treat candida infections. however, the indiscriminate use of this antimycotic therapy has favored the emergence of resistant isolates. mutations in the erg11 gene have been described as one of the primary mechanisms of resistance in candida species.201623402828
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
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
[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
[physiological function in torulopsis glabrata--a review].a multi-vitamin auxotrophic yeast of torulopsis glabrata was the most competitive strain for industrial production of pyruvate. given its genomic characterizations and physiological functions, it was an efficient way to redirect carbon flux to the target metabolites through manipulating nutritional and environmental conditions, intracellular cofactor form and level. in this review, we summarized the progress on the elucidation and manipulation of physiological function of t. glabrata. furthermor ...201223383501
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
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
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
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
nicotinic acid modulates legionella pneumophila gene expression and induces virulence traits.in response to environmental fluctuations or stresses, bacteria can activate transcriptional and phenotypic programs to coordinate an adaptive response. the intracellular pathogen legionella pneumophila converts from a noninfectious replicative form to an infectious transmissive form when the bacterium encounters alterations in either amino acid concentrations or fatty acid biosynthesis. here, we report that l. pneumophila differentiation is also triggered by nicotinic acid, a precursor of the c ...201323319553
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
gross karyotypic and phenotypic alterations among different progenies of the candida glabrata cbs138/atcc2001 reference strain.genomic plasticity is a mechanism for adaptation to environmental cues such as host responses and antifungal drug pressure in many fungi including the human pathogenic yeast candida glabrata. in this study we evaluated the phenotypic and genotypic stability of the world-wide used c. glabrata reference strain cbs138/atcc2001 under laboratory conditions. a set of ten lineages of this wild type strain and genetically modified progenies were obtained from different scientific laboratories, and analy ...201223284942
hydroxyurea therapy in sickle cell anemia patients aids to maintain oral fungal colonization balance.the aim of this study was to evaluate the frequency of candida species and presence of lesions in the oral cavity of patients with sickle cell anemia (ss).201223278631
design, spectral characterization and biological studies of transition metal(ii) complexes with triazole schiff bases.a new series of three biologically active triazole derived schiff base ligands l(1)-l(3) have been synthesized in equimolar reaction of 3-amino-1h-1,2,4-triazole with pyrrol-2-carboxaldehyde, 4-bromo-thiophene-2-carboxaldehyde, and 5-iodo-2-hydroxy benzaldehyde. the prepared schiff bases were used for further complex formation reaction with different metal elements like co(ii), ni(ii), cu(ii) and zn(ii) as chlorides by using a molar ratio of ligand:metal as 2:1. the structure and bonding nature ...201223277183
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
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
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
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
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
evolutionary rate covariation in meiotic proteins results from fluctuating evolutionary pressure in yeasts and mammals.evolutionary rates of functionally related proteins tend to change in parallel over evolutionary time. such evolutionary rate covariation (erc) is a sequence-based signature of coevolution and a potentially useful signature to infer functional relationships between proteins. one major hypothesis to explain erc is that fluctuations in evolutionary pressure acting on entire pathways cause parallel rate changes for functionally related proteins. to explore this hypothesis we analyzed erc within dna ...201223183665
prevalence of chronic hyperplasic candidiasis. its association to risk factors in an oral medicine service in rosario, argentina.chronic hyperplasic candidiasis (chc) is one of clinical forms of infection caused by fungi from genus candida, basically candida albicans, and less frequently by other species of the genus, such as candida tropicalis, candida guilliermondii, candida glabrata, candida parapsilosis, candida dubliniensis y candida krusei.201223177812
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
[yeast colonization of urinary catheters and the significance of biofilm formation].urinary catheters are colonized by a wide range of microorganisms, including numerous yeasts. the catheters are usually colonized by more microbial species forming a community - multispecies biofilm. catheter colonization usually does not affect the patient's clinical status in any significant way. on the other hand, the biofilm can become a source of endogenous infection and its presence can affect functionality of the catheter and formation of urinary stones. material a201223172023
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
candiduria in haematologic malignancy patients without a urinary catheter: nothing more than a frailty marker?there is scarcity of data regarding significance of candiduria in patients with haematologic malignancies and its association with invasive candidiasis. to that end, we retrospectively evaluated all hospitalised, non-intensive care unit patients with haematologic malignancies and candiduria during a 10-year period (2001-2011). to decrease the possibility of bladder colonisation and sample contamination, we excluded all patients with candiduria who had urinary catheters and those with concomitant ...201323170870
chemical composition and biological activities of essential oil from hyptis crenata growing in the brazilian cerrado.essential oils from species of the genus hyptis are well-known for their significant biological properties, including antimicrobial and acaricidal activities. the essential oil from the aerial parts of h. crenata was obtained by hydrodistillation; bomeol (17.8%), 1,8-cineol (15.6%) and p-cimene (7.9%) were characterized by gc-ms as its major constituents. the essential oil was evaluated in vitro for its antimicrobial activities against six fungal and five bacterial strains, by measuring the resp ...201223157018
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
rapid identification of drug resistant candida species causing recurrent vulvovaginal candidiasis.some yeast agents including candida albicans, candida tropicalis and candida glabrata have a role in recurrent vulvovaginal candidiasis. we studied the frequency of both common and recurrent vulvovaginal candidiasis in symptomatic cases which were referred to urmia medical sciences university related gynecology clinics using morphologic and molecular methods. the aim of this study was the identification of candida species isolated from recurrent vulvovaginal candidiasis cases using a rapid and r ...201223149354
candida glabrata sepsis associated with chorioamnionitis in an in vitro fertilization pregnancy: case report and review.we report a case of candida glabrata sepsis associated with chorioamnionitis in an in vitro fertilization-assisted pregnancy. there is a strong association between c. glabrata chorioamnionitis and assisted fertility techniques. candida glabrata chorioamnionitis presents unique management challenges.201323143095
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
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
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
evaluation of caspofungin susceptibility testing by the new vitek 2 ast-ys06 yeast card using a unique collection of fks wild-type and hot spot mutant isolates, including the five most common candida species.fks mutant isolates associated with breakthrough or failure cases are emerging in clinical settings. discrimination of these from wild-type (wt) isolates in a routine laboratory setting is complicated. we evaluated the ability of caspofungin mic determination using the new vitek 2 ast-y06 yeast susceptibility card to correctly identify the fks mutants from wt isolates and compared the performance to those of the clsi and eucast reference methods. a collection of 98 candida isolates, including 31 ...201323089746
mutants in the candida glabrata glycerol channels are sensitized to cell wall stress.many fungal species use glycerol as a compatible solute with which to maintain osmotic homeostasis in response to changes in external osmolarity. in saccharomyces cerevisiae, intracellular glycerol concentrations are regulated largely by the high osmolarity glycerol (hog) response pathway, both through induction of glycerol biosynthesis and control of its flux through the plasma membrane fps1 glycerol channel. the channel activity of fps1 is also controlled by a pair of positive regulators, rgc1 ...201223087370
identification of fungicidal 2,6-disubstituted quinolines with activity against candida biofilms.we have identified two subseries of 2,6-disubstituted quinolines, consisting of 6-amide and 6-urea derivatives, which are characterized by fungicidal activity against candida albicans with minimal fungicidal concentration (mfc) values < 15 µm. the 6-amide derivatives displayed the highest fungicidal activity against c. albicans, in particular compounds 1, 5 and 6 characterized by mfc values of 6.25-12.5 µm. compounds 1 and 5 of this series displayed fungicidal activity against the emerging patho ...201223079495
neck rotation and neck mimic docking in the noncatalytic kar3-associated protein vik1.kar3vik1 is a heterodimeric kinesin with one catalytic subunit (kar3) and one noncatalytic subunit (vik1).201223043140
structural basis for promiscuity and specificity during candida glabrata invasion of host epithelia.the human pathogenic yeast candida glabrata harbors more than 20 surface-exposed, epithelial adhesins (epas) for host cell adhesion. the epa family recognizes host glycans and discriminates between target tissues by their adhesin (a) domains, but a detailed structural basis for ligand-binding specificity of epa proteins has been lacking so far. in this study, we provide high-resolution crystal structures of the epa1a domain in complex with different carbohydrate ligands that reveal how host cell ...201223035251
two clinical isolates of candida glabrata exhibiting reduced sensitivity to amphotericin b both harbor mutations in erg2.two novel isolates of candida glabrata exhibiting reduced sensitivity to amphotericin b (mic, 8 μg ml(-1)) were found to be erg2 mutants, wherein δ(8)-sterol intermediates comprised >90% of the total cellular sterol fraction. both harbored an alteration at thr(121) in erg2; the corresponding residue (thr(119)) in saccharomyces cerevisiae is essential for sterol δ8-δ7 isomerization. this constitutes the first report of c. glabrata harboring mutations in erg2 and exhibiting reduced sensitivity to ...201223027188
fks1 and fks2 are functionally redundant but differentially regulated in candida glabrata: implications for echinocandin resistance.the echinocandins caspofungin, micafungin, and anidulafungin, inhibitors of cell wall β-1,3-glucan synthesis, were recently elevated to first-line agents for treating infections due to the azole-refractory yeast candida glabrata. in candida albicans, echinocandin resistance is strictly associated with mutations in fks1, a large integral membrane protein and putative β-1,3-glucan synthase, while mutations in both fks1 and its paralog fks2 (but not fks3) have been associated with resistance in c. ...201223027185
candida glabrata: an unusual fungal infection following a total hip replacement.a 60-year-old woman, after a femoral neck fracture and joint replacement, underwent a girdlestone's procedure and received aggressive antimicrobial therapy in order to completely eradicate the fungal infection candida glabrata. in the majority of such cases, a revised hip arthroplasty would be considered following debridement. however, due to the recurrence of this infection and a key associated risk factor, radical removal with concurrent drug therapy was the only option.201223008369
clinical characteristics of candidaemia in adults with haematological malignancy, and antimicrobial susceptibilities of the isolates at a medical centre in taiwan, 2001-2010.during the period 2001-2010, a total of 154 episodes of candidaemia were noted in 111 of 2574 patients with haematological malignancies at the national taiwan university hospital (taipei, taiwan). patients with acute lymphoblastic leukaemia had a significantly higher rate of candidaemia than patients with other haematological malignancies (odds ratio=2.69; p<0.001). candida tropicalis was the most common candida species (n=51; 46%), followed by candida albicans (n=35; 32%), candida parapsilosis ...201223006521
distribution of fluconazole-resistant candida bloodstream isolates among hospitals and inpatient services in israel.the emergence of fluconazole-resistant candida (frc) is worrisome, but little is known about susceptibility patterns in different nosocomial settings. we prospectively analysed candida bloodstream isolates in 18 medical centres in israel (six tertiary-care and 12 community hospitals). the study included 444 episodes of candidaemia (450 patient-specific isolates, 8.5% fluconazole-resistant). institutional frc bloodstream infection rates correlated with annual inpatient days, and were strongly ass ...201323005038
fluconazole resistance in candida glabrata is associated with increased bud formation and metallothionein production.virulence associated with fluconazole (fl) resistance in candida glabrata is a global problem and has not been well characterized at the proteome level. in this study, a stable fl-resistant (mic >256 µg ml(-1)) strain of c. glabrata was generated on agar containing fl. eight phenotypic mutants were characterized by contour-clamped homogeneous electrophoretic field analysis and two-dimensional page. the secondary derivatives of c. glabrata yielded four distinct genotypes with varying chromosomal ...201323002065
results from a prospective, international, epidemiologic study of invasive candidiasis in children and neonates.candida species are the third most common cause of pediatric health care-associated bloodstream infection in the united states and europe. to our knowledge, this report from the international pediatric fungal network is the largest prospective, multicenter observational study dedicated to pediatric and neonatal invasive candidiasis.201222982980
[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
metal based new triazoles: their synthesis, characterization and antibacterial/antifungal activities.a series of new triazoles and their oxovanadium(iv) complexes have been synthesized, characterized and evaluated for antibacterial/antifungal properties. the new schiff bases ligands (l(1))-(l(5)) were prepared by the condensation reaction of 3,5-diamino-1,2,4-triazole with 2-hydroxy-1-naphthaldehyde, pyrrole-2-carboxaldehyde, pyridine-2-carboxaldehyde, 2-acetyl pyridine and 2-methoxy benzaldehyde. the structures of the ligands have been established on the basis of their physical, spectral (ir, ...201222982389
colonization of the oral cavity by yeasts in patients with chronic renal failure undergoing hemodialysis.to determine the frequency of yeast in the oral cavity of patients with chronic renal failure, undergoing hemodialysis (pcrfh); identification and antifungal susceptibility profile of yeast and demographic profile of patients.201322978344
effectiveness of the association of 2 probiotic strains formulated in a slow release vaginal product, in women affected by vulvovaginal candidiasis: a pilot study.vulvovaginal candidiasis (vvc) is the second most common cause of vaginitis after bacterial vaginosis, and it is diagnosed in up to 40% of women with vaginal complaints in the primary care setting. among candida spp., candida albicans is the most common infectious agent. the treatment of choice for uncomplicated vvc is achieved with single-dose or short-course therapy in over 90% of cases. several topical and oral drugs are available, without evidence for superiority of any agent or route of adm ...201222955364
hartmannella vermiformis can promote proliferation of candida spp. in tap-water.candida yeasts colonize humans' oral cavities as commensals or opportunistic pathogens. they may be isolated from water circulating in dental unit waterlines mixed with saliva traces mainly because of dysfunction of anti-retraction valves. free-living amoebae (fla), like hartmannella vermiformis, are frequently found in aquatic environments and they have also been already isolated from dental unit waterlines. they can be implicated as reservoir for pathogens or directly in infections. this work ...201222951330
optimizing echinocandin dosing and susceptibility breakpoint determination via in vivo pharmacodynamic evaluation against candida glabrata with and without fks mutations.echinocandins are a preferred therapy for invasive candidiasis due to their potency and broad spectrum. resistance, especially in candida glabrata, is an emerging threat to their use. pharmacodynamic (pd) studies examining reduced susceptibility secondary to fks mutations in c. glabrata are lacking. the current study explored pd targets for anidulafungin, caspofungin, and micafungin in an in vivo invasive candidiasis model against 11 c. glabrata isolates with known or putative fks mutations. the ...201222948870
de novo generation of a phosphate starvation-regulated promoter in candida glabrata.what steps are required for a promoter to acquire regulation by an environmental condition? we address this question by examining a promoter in candida glabrata that is regulated by phosphate starvation and the transcription factor pho4. the gene pmu2 encodes a secreted acid phosphatase that resulted from gene duplication events not present in other ascomycetes, and only this gene of the three paralogs has acquired pho4 regulation. we observe that the pmu2 promoter from c. glabrata is not functi ...201222938599
[candida glabrata : pathogenicity and therapy update].chronic recurrent vulvovaginal candidiasis caused by candida glabrata is still rare in comparison to c. albicans infection, but therapy remains more difficult. standard agents as fluconazole or itraconazole often fail, as well as the newer systemic triazoles like voriconazole or posaconazole. micafungin is a new echinocandin drug with a wide antifungal spectrum including rare candida species. no clinical trials with micafungin in chronic recurrent vulvovaginal candidiasis have been undertaken. w ...201222925897
synthesis, crystal structure, characterisation, and antifungal activity of 3-thiophene aldehyde semicarbazone (3stch), 2,3-thiophene dicarboxaldehyde bis(semicarbazone) (2,3bstch2) and their nickel (ii) complexes.the reaction of nickel (ii) chloride and bromide with 3-thiophene aldehyde semicarbazone (3stch) and 2,3-thiophene dicarboxaldehyde bis(semicarbazone) (2,3bstch(2)) leads to the formation of a series of new complexes: [nicl(2)(3stch)(2)], [nibr(2)(3stch)(2)], [nicl(2,3bstch(2))(h(2)o)]cl, and [nibr(2,3bstch(2))(h(2)o)]br respectively. the crystal structures of the two ligands 3stch, 2,3bstch(2) and of the complex [nibr(2,3bstch(2))(h(2)o)]br have been determined by x-ray diffraction methods. for ...201222922309
predisposing factors for oropharyngeal colonization of yeasts in human immunodeficiency virus-infected patients: a prospective cross-sectional study.oropharyngeal candidiasis continues to be a major opportunistic infection in human immunodeficiency virus (hiv)-infected patients. the objectives of this study were to investigate the prevalence, associated factors, and microbiologic features for oropharyngeal yeast colonization in hiv-infected patients.201322921200
is the incidence of candidemia caused by candida glabrata increasing in brazil? five-year surveillance of candida bloodstream infection in a university reference hospital in southeast brazil.from 2006 to 2010, a retrospective study was conducted in a university referral tertiary care hospital to study the frequency and distribution of candida species in different medical specialties. the use of mechanical ventilation, central venous catheter, and urinary catheter were recorded per 1,000 patient-days and the use of antifungals was calculated using defined daily dose (ddd). a total of 313 episodes were identified and the overall incidence was 0.54 (0.41-0.71) episodes per 1,000 patien ...201322920712
functional genomic analysis of candida glabrata-macrophage interaction: role of chromatin remodeling in virulence.fungal septicemia is an increasingly common complication of immunocompromised patients worldwide. candida species are the leading cause of invasive mycoses with candida glabrata being the second most frequently isolated candida species from intensive care unit patients. despite its clinical importance, very little is known about the mechanisms that c. glabrata employs to survive the antimicrobial and immune response of the mammalian host. here, to decipher the interaction of c. glabrata with the ...201222916016
crs-mis in candida glabrata: sphingolipids modulate echinocandin-fks interaction.infections with the azole-refractory yeast candida glabrata are now commonly treated with the echinocandins caspofungin (csf) or micafungin (mcf). true resistance (>  32-fold decreased susceptibility) to these lipopeptide inhibitors of cell wall synthesis is rare and strictly associated with mutations in integral membrane proteins fks1 or fks2. in contrast, mutants exhibiting 4- to 32-fold csf reduced susceptibility (crs) were readily selected in vitro, and surprisingly demonstrated 4- to 32-fol ...201222909030
changes in incidence and antifungal drug resistance in candidemia: results from population-based laboratory surveillance in atlanta and baltimore, 2008-2011.candidemia is common and associated with high morbidity and mortality; changes in population-based incidence rates have not been reported.201222893576
[efficacy of voriconazole treatment in chronic vulvovaginal candidosis due to candida glabrata].vulvovaginal candidosis is a common infection in young women, and it is associated with high morbidity and high health costs.201322885618
a review of candida species causing blood stream infection.the incidence of candidemia has been on a rise worldwide. the epidemiology of invasive fungal infections in general and of candidemia in particular has changed in the past three decades because of a variety of factors like the aids epidemic, increased number of patients receiving immunosuppressive therapy for transplantation and the increasing use of antimicrobials in the hospital setups and even in the community. the important risk factors for candidemia include use of broad-spectrum antimicrob ...201222885191
species identification and antifungal susceptibility testing of candida bloodstream isolates from population-based surveillance studies in two u.s. cities from 2008 to 2011.between 2008 and 2011, population-based candidemia surveillance was conducted in atlanta, ga, and baltimore, md. surveillance had been previously performed in atlanta in 1992 to 1993 and in baltimore in 1998 to 2000, making this the first population-based candidemia surveillance conducted over multiple time points in the united states. from 2,675 identified cases of candidemia in the current surveillance, 2,329 candida isolates were collected. candida albicans no longer comprised the majority of ...201222875889
synthesis and comparative study on the antimicrobial activity of hybrid materials based on silver nanoparticles (agnps) stabilized by polyvinylpyrrolidone (pvp).hybrid materials based on polyvinylpyrrolidone (pvp) with silver nanoparticles (agnps) were synthesized applying two different strategies based on thermal or chemical reduction of silver ions to silver nanoparticles using pvp as a stabilizer. the formation of spherical silver nanoparticles with diameter ranging from 9 to 16 nm was confirmed by tem analysis. uv-vis and ftir spectroscopy were also applied to confirm the successful formation of agnps. the antibacterial activity of the synthesized a ...201122837793
rapid identification of histoplasma capsulatum directly from cultures by multiplex pcr.the multiplex pcr developed from a suspension of the yeast fungi correctly identified fifty-one clinical of h. capsulatum var. capsulatum strains isolated from clinical samples and soil specimens. the multiplex pcr was developed by combining two pairs of primers, one of them was specific to the h. capsulatum and the other one, universal for fungi, turned out to be specific to h. capsulatum, regardless of the fungus isolate studied. primers designed to amplify a region of about 390-bp (hc i-hc ii ...201222821346
association between incidence of candidaemia and consumption of antifungal agents at a medical centre in taiwan.this study investigated the correlations between consumption of antifungal agents and species distribution in candidaemia. the incidence of patients with community-acquired candidaemia (cac) (per 1000 admissions) and healthcare-associated candidaemia (hcac) (per 1000 admissions) as well as data on annual consumption [defined daily doses (ddd)/1000 patient-days] of various antifungal agents at a medical centre in taiwan from 2000 to 2010 were evaluated. a total of 2682 episodes of candidaemia wer ...201222819796
in vitro adhesion of candida glabrata to denture base acrylic resin modified by glow-discharge plasma treatment.this study evaluated the potential of plasma treatments to modify the surface chemistry and hydrophobicity of a denture base acrylic resin to reduce the candida glabrata adhesion. specimens (n = 54) with smooth surfaces were made and divided into three groups (n = 18): control - non-treated; experimental groups - submitted to plasma treatment (ar/50 w; aat/130 w). the effects of these treatments on chemical composition and surface topography of the acrylic resin were evaluated. surface free ener ...201322809146
the effect of silver nanoparticles and nystatin on mixed biofilms of candida glabrata and candida albicans on acrylic.the aim of this study was to compare biofilm formation by candida glabrata and candida albicans on acrylic, either individually or when combined (single and dual species) and then examine the antimicrobial effects of silver nanoparticles and nystatin on these biofilms. candidal adhesion and biofilm assays were performed on acrylic surface in the presence of artificial saliva (as) for 2 h and 48 h, respectively. candida glabrata and c. albicans adherence was determined by the number of colony for ...201322803822
determination of the effect of nd:yag laser irradiation through dentinal tubules on several oral pathogens.the effects of nd:yag laser irradiations at different power settings on several oral pathogens were evaluated. a total of 252 dentin samples were divided into seven groups consisting of 36 dentin specimens each. in each group, 9 of the 36 specimens were used as controls, thereby including a control in every group. the remaining 27 specimens were divided into three subgroups consisting of nine specimens according to different nd:yag laser settings (1.5, 1.8, and 2 w). each group was inoculated on ...201322767323
increased diversity of fungal flora in the vagina of patients with recurrent vaginal candidiasis and allergic rhinitis.recurrent vaginal candidiasis (rvc) is considered to be a hypersensitivity disorder that is associated with allergic rhinitis (ar) in immune deficiencies; however, whether or not the composition of the vaginal fungal flora in patients with ar and rvc is altered and if such alterations in patients with ar are associated with the development of rvc remain unclear. in the present study, a cultivation-independent method with the 18s rrna gene clone library was used to analyze the diversity and compo ...201222767123
candida glabrata: an emerging pathogen in brazilian tertiary care hospitals.candida glabrata is an infrequent cause of candidemia in brazilian public hospitals. we investigated putative differences in the epidemiology of candidemia in institutions with different sources of funding. prospective laboratory-based surveillance of candidemia was conducted in seven private and two public brazilian tertiary care hospitals. among 4,363 episodes of bloodstream infection, 300 were caused by candida spp. (6.9%). incidence rates were significantly higher in public hospitals, i.e., ...201322762208
the presence of an fks mutation rather than mic is an independent risk factor for failure of echinocandin therapy among patients with invasive candidiasis due to candida glabrata.echinocandins are frontline agents against invasive candidiasis (ic), but predictors for echinocandin therapeutic failure have not been well defined. mutations in candida fks genes, which encode the enzyme targeted by echinocandins, result in elevated mics and have been linked to therapeutic failures. in this study, echinocandin mics by broth microdilution and fks1 and fks2 mutations among c. glabrata isolates recovered from patients with ic at our center were correlated retrospectively with ech ...201222751546
risk factors for candidemia with non-albicans candida spp. in intensive care unit patients with end-stage renal disease on chronic hemodialysis.the objective of this study was to describe factors associated with bloodstream infections (bsis) with non-albicans candida species (nac), compared with candida albicans bsis, and antifungal susceptibility patterns in adult intensive care unit (icu) patients with chronic renal failure undergoing hemodialysis. to the best of our knowledge, this is the first study to report the potential factors for nac candidemia in icu patients with end-stage renal disease on chronic hemodialysis.201222748623
evaluation of reference genes for real-time quantitative pcr studies in candida glabrata following azole treatment.the selection of stable and suitable reference genes for real-time quantitative pcr (rt-qpcr) is a crucial prerequisite for reliable gene expression analysis under different experimental conditions. the present study aimed to identify reference genes as internal controls for gene expression studies by rt-qpcr in azole-stimulated candida glabrata.201222747760
primary retroperitoneal abscess caused by candida glabrata.clinically, retroperitoneal abscesses present insidiously and the diagnosis may be delayed. this, with inadequate drainage, may result in increased morbidity and mortality. most cases result from a renal or gastrointestinal process, but in a small number of patients there is no identifiable source and the abscess is designated as "primary." most retroperitoneal abscesses are polymicrobial, and cultures often reveal organisms such as proteus mirabilis, staphylococcus species, peptostreptococcus, ...201222739567
occurrence of killer yeasts in isolates of clinical origin.a total of 1 025 strains belonging to different candida species of clinical origin were evaluated for their killer activity against sensitive strains of saccharomyces cerevisiae. isolates were identified by standard morphological and biochemical analyses. for the evaluation of the killer activity, potential killer isolates were streaked on plates previously seeded with the sensitive strain. a total of 52 candida isolates (5%) exhibited killer activity against both sensitive yeast strains. the oc ...201222735852
voriconazole inhibits biofilm formation in different species of the genus candida.to determine the ability of voriconazole to inhibit the formation of biofilms.201222733651
carbonic anhydrase regulation and co(2) sensing in the fungal pathogen candida glabrata involves a novel rca1p ortholog.carbon dioxide (co2) is a ubiquitous gas present at 0.0391% in atmospheric air and 5.5% in human blood. it forms part of numerous carboxylation and decarboxylation reactions carried out in every cell. carbonic anhydrases (ca) enhance the hydration of co2 to generate bicarbonate, which is subsequently used in cellular metabolism. in microorganisms, including the yeasts candida albicans and saccharomyces cerevisiae, inactivation of ca leads to a growth defect in air, which is complemented in an at ...201322727373
relationship between respiration deficiency and azole resistance in clinical candida glabrata.candida glabrata has become a leading cause of invasive infections around the world and is exhibiting growing resistance to azole antifungals. to study the mechanism of its azole resistance, we analyzed the efflux pumps and found well known increased efflux expression and low metabolic state in all azole-resistant strains. the latter finding led us to further investigate the relationship between respiration status and azole antifungal susceptibility in clinical c. glabrata by growing them on gly ...201222713096
replacement of the methylene of dihydrochalcones with oxygen: synthesis and biological evaluation of 2-phenoxyacetophenones.with the aim of finding new bioactive compounds, a series of phenoxyacetophenone derivatives 2 were designed and synthesized as oxygen analogs of dihydrochalcones. also, phenoxyacetophenones were converted to (z)-oxime derivatives 3 and their geometry were characterized by ¹h-nmr spectroscopy. the in vitro antifungal activity of compounds 2 and 3 was evaluated against candida albicans, candida glabrata, saccharomyces cerevisiae, and aspergillus niger using micro-dilution method. in general, oxim ...201222712717
candida species: new insights into biofilm formation.biofilms of candida albicans, candida parapsilosis, candida glabrata and candida tropicalis are associated with high indices of hospital morbidity and mortality. major factors involved in the formation and growth of candida biofilms are the chemical composition of the medical implant and the cell wall adhesins responsible for mediating candida-candida, candida-human host cell and candida-medical device adhesion. strategies for elucidating the mechanisms that regulate the formation of candida bio ...201222702528
antifungal activity of arctotis arctotoides (l.f.) o. hoffm. and gasteria bicolor haw. against opportunistic fungi associated with human immunodeficiency virus/acquired immunodeficiency syndrome.in south africa where many patients are immunocompromised as a result of the aids pandemic, opportunistic fungal infections such as candidiasis caused mainly by candida albicans are common. arctotis arctotoides and gasteria bicolor are two plants which are frequently and commonly used in traditional medicine in the treatment of hiv patients.201222701287
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