Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CANDIDA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,495 records · Page 83Linked to original sources

The risk of positive cultures for Candida in the critically ill patient.

It is frequently stated that a positive fungal culture is of little clinical significance unless the culture is obtained on repetitive blood specimens. We analyzed the mortality associated with a positive culture for Candida species in ICU patients from several locations over a 3-month period. Criteria for inclusion in this study were: (1) residence in the ICU for at least 4 days, (2) no GI tract alimentation during this period, and (3) administration of at least one antibiotic during this period. Forty-four patients fit these criteria; 23 had positive Candida cultures from at least one site and 12 (52%) died. Four of 21 patients (19%) who did not grow Candida died. Cultures of urine and sputum were most likely to be positive. Positive cultures from the urine, sputum, or wound were associated with at least a 50% mortality. This suggests that routine sputum and urine cultures may be of substantial clinical therapeutic and prognostic significance. Two patients had positive blood cultures and both died. No single class of antibiotics, surgical complications or underlying disease predisposed to these results. It is concluded that the presence of a single positive culture for Candida from any site in the critically ill surgical patient kept without GI alimentation and on any antibiotic is a grave prognostic sign which requires further attention.

Aged↗

Phagocytosis of Candida albicans induces apoptosis of human neutrophils.

Neutrophil-mediated inflammation is terminated through the programmed cell death or apoptosis of the neutrophil, a process that can be inhibited by soluble mediators released during an inflammatory response. It has been reported, however, that the phagocytosis of intact bacteria can accelerate apoptosis. We evaluated the effects of the phagocytosis of a common nosocomial pathogen, Candida albicans, on the expression of apoptosis. Phagocytosis of killed Candida induced a dose-dependent increase in the apoptosis of normal neutrophils after 18 h of in vitro culture, from 40.7+/-9.1% to 81.7+/-4.5%, while supernatants from neutrophil:Candida co-cultures actually inhibited apoptosis. Induction of apoptosis was not dependent on phagocytosis, since opsonization of yeast with serum failed to increase apoptosis, while inhibition of phagocytosis with latrunculin B resulted in a slightly increased apoptotic rate. Increased apoptosis induced by Candida was associated with increased activity of the membrane-associated apoptotic enzyme, caspase 8, and with increased expression of the active form of the key executioner caspase, caspase 3. Increased apoptosis was associated with depletion of intracellular glutathione (GSH), and could be inhibited by the addition of exogenous GSH. These data demonstrate an important physiologic role for host-pathogen interactions in the resolution of inflammation and suggest that the response to an invading pathogen is an important stimulus to the restoration of normal immunologic homeostasis.

Apoptosis↗

Candida aquaetextoris sp. nov., a new species of yeast occurring in sludge from a textile industry wastewater treatment plant in Tuscany, Italy.

We describe Candida aquaetextoris, a new yeast species isolated from sludge that accumulates at the main wastewater treatment facility which processes discharges from textile factories located in the Prato metropolitan district, northern Tuscany, Italy. This yeast degrades 4-(1-nonyl)phenol, a toxic intermediate originating from the microbial attack of nonylphenol polyethoxylates, which are nonionic surfactants largely used in leather and textile industries. In the investigation we employed conventional and molecular taxonomy techniques to compare the new isolate to strains of physiologically similar species, such as Candida maltosa and Candida tropicalis, as well as strains of quite phenotypically different species, such as Candida haemulonii. The results demonstrate that the yeast which we identified represents a separate taxon. The type strain of C. aquaetextoris is strain Lmar1, which has been deposited in the Industrial Yeast Collection of the Division of Applied Microbiology, Department of Plant Biology, University of Perugia, Perugia, Italy, as strain DBVPG 6732.

Candida↗

Susceptibility to fluconazole of Candida clinical isolates determined by FUN-1 staining with flow cytometry and epifluorescence microscopy.

The susceptibility of clinical Candida isolates to fluconazole was assayed by flow cytometry (FCM) and epifluorescence microscopy (EFM), with FUN-1 staining. In all, 25 clinical isolates of Candida spp. (12 sensitive, 3 dose-dependently sensitive and 10 resistant to fluconazole according to the NCCLS M27-A protocol) were treated with increasing concentrations of fluconazole during 1 or 2 h staining with FUN-1 for 30 min and analysed, respectively, by FCM at 575 nm (FL2) and by EFM. Fluconazole-susceptible strains showed an increased accumulation of FUN-1 in comparison with controls as determined by FCM and a reduced metabolic processing of the probe, confirmed by EFM. Conversely, resistant strains showed decreased FUN-1 staining and were able to process the probe. The fluconazole minimal inhibitory concentrations (MICs) determined by FCM or EFM after FUN-1 staining compared very well with the corresponding values determined by the M27-A protocol, indicating that FUN-1 staining can be used as an alternative to the conventional method. MIC values of resistant strains, with the exception of C. krusei, were lower when treatment with fluconazole followed pre-incubation with 0.1 mM sodium azide, a concentration known to inhibit the activity of efflux pumps. These results show that FUN-1 staining can be used as an alternative and rapid method for the assessment of susceptibility of Candida clinical isolates to fluconazole. Furthermore, the results suggest that resistance of Candida cells to fluconazole, with the exception of C. krusei strains, is likely to be due to the activity of efflux pumps.

Antifungal Agents↗

Mechanisms of association of Candida albicans with intestinal mucosa.

The association of Candida albicans with gastrointestinal (GI) mucosal surfaces was studied in vitro and in vivo. The caecal mucosal surfaces from antibiotic-treated and untreated control mice challenged orally with C. albicans revealed that large numbers of C. albicans were associated with the intestinal epithelium of antibiotic-treated mice but not with that of the control mice that possessed an indigenous wall-associated bacterial flora. Moreover, Candida cells only penetrated deep into the mucosa of animals in which the ecology of the intestinal microflora had been disrupted. In mice given antibiotics, C. albicans was associated with the mucosa of all areas of the GI tract; the caecal mucosa had the most associated Candida, whereas the stomach and small intestine had very few associated yeasts. Further examination of caecal mucosa from antibiotic-treated mice showed that C. albicans associated with the mucosa by at least five distinct mechanisms. These included: adhesion to epithelium, adhesion to mucus, co-adhesion to adherent fungi, co-adhesion to adherent bacteria, and entrapment in the mucous gel overlying the epithelium. The cell-surface hydrophobicity of C. albicans also was examined and found not to play a role in Candida adhesion to intestinal mucosa. The predominant association mechanisms appeared to be entrapment in the mucous gel, and adhesion to mucus and the epithelium. The ecological and pathological significance of co-adhesion by C. albicans to attached organisms is unclear but it may be important in the initiation of mucosal lesions.

Animals↗

An alpha 5 beta 1-like integrin receptor mediates the binding of less pathogenic Candida species to fibronectin.

The present study was undertaken to investigate whether less pathogenic Candida species (C. tropicalis, C. stellatoidea, C. krusei and C. glabrata) express a fibronectin receptor (FNr) antigenically related to alpha 5 beta 1 integrin, which mediates their binding to fibronectin (FN). By flow cytometric analysis, a monoclonal antibody (MAb) directed against human alpha 5 integrin subunit (clone SAM-1) and two different antisera to FNr positively stained C. tropicalis, C. stellatoidea and C. glabrata, with the greatest expression observed for C. tropicalis. No or only marginal immunoreactivity was found on C. krusei. C. tropicalis, C. stellatoidea, C. glabrata, but not C. krusei yeasts specifically adhered to FN; higher levels of adhesion were found for C. tropicalis and C. stellatoidea with respect to C. glabrata. Less pathogenic Candida spp. bound to the Arg-Gly-Asp (RGD) containing 120-kDa fragment of FN and adhesion to intact FN was markedly inhibited by Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), but not by Gly-Arg-Gly-Glu-Ser-Pro (GRGESP) peptides. In addition, anti-alpha 5 SAM-1 MAb and both anti-FNr antisera strongly blocked binding of less pathogenic Candida spp. to FN. Overall, these results indicate that less pathogenic Candida spp., including C. tropicalis, C. stellatoidea and C. glabrata, express a receptor antigenically related to alpha 5 beta 1 integrin which mediates their adhesion to FN.

Amino Acid Sequence↗

Ground red hot pepper agar in the isolation of yeasts of Candida spp.

The purpose of this study was to investigate and determine the value of a novel, simple and inexpensive selective medium for isolation of yeasts of Candida spp. - ground red hot pepper agar (GRHP). The study compared GRHP and Sabouraud dextrose agar (SDA), an insufficiently selective medium routinely used for primary isolation of yeasts. The comparison was based on qualitative and quantitative characterisation of growth of 25 bacterial strains, measurement of growth of 22 yeast strains and testing on clinical specimens. Qualitative tests on bacteria showed either significantly less growth on GRHP than on SDA, or no growth on GRHP. Quantitative tests confirmed these results; the number of colonies of all tested bacterial species and strains on GRHP was significantly lower than on SDA. With regard to the isolation of Candida spp., GRHP had the same properties as SDA. Statistical analysis showed no significant differences in the growth of Candida spp. and strains on the two media. All these results were confirmed by tests on clinical material. The results clearly show that GRHP agar is an economical medium for the isolation of yeasts of Candida spp., with excellent selectivity.

Bacteria↗

Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals.

Atypical oral Candida isolates were recovered from 60 HIV-infected and three HIV-negative individuals. These organisms were germ-tube-positive and produced abundant chlamydospores which were frequently arranged in triplets or in contiguous pairs. They belonged to C. albicans serotype A and had atypical carbohydrate assimilation profiles. Fingerprinting the genomic DNA of a selection of these organisms with the C. albicans-specific probe 27A and five separate oligonucleotides, homologous to eukaryotic microsatellite repeat sequences, demonstrated that they had a very distinct genomic organization compared to C. albicans and C. stellatoidea. This was further established by random amplified polymorphic DNA (RAPD) and karyotype analysis. Comparison of 500 bp of the V3 variable region of the large ribosomal subunit genes from nine atypical isolates and the corresponding sequences determined from C. albicans, C. stellatoidea, C. tropicalis, C. parapsilosis, C. glabrata, C. kefyr and C. krusei showed that they atypical organisms formed a homogeneous cluster (100% similarity) that was significantly different from the other Candida species analysed, but was most closely related to C. albicans and C. stellatoidea. These genetic data combined with the phenotypic characteristics of these atypical organisms strongly suggest that they constitute a novel species within the genus Candida for which the name Candida dubliniensis is proposed.

AIDS-Related Opportunistic Infections↗

Anti-Candida activity of a novel killer toxin from the yeast Williopsis mrakii.

A screening of putative killer yeast strains showed that spore-forming ascomycetous yeasts of the genera Pichia and Williopsis displayed the broadest range of activity against sensitive strains of Candida spp. and Saccharomyces cerevisiae. Williopsis mrakii (NCYC 500) showed extensive anti-Candida activity against strains isolated from clinical specimens. W. mrakii killer factor was produced in minimal media as a function of growth and its activity reached constant levels as cells entered stationary phase. The proteinaceous killer toxin was found to be unstable without a specific range of temperature and pH (above 30 degrees C and pH 4.0), and further analysis showed that the active toxin molecule was an acidic polypeptide with a relative molecular mass between 1.8-5.0 kDa. At critical concentrations the killer factor exerted a greater effect on stationary phase cells of Candida than cells from an exponential phase of growth. At low concentrations, the killer toxin produced a fungistatic effect on sensitive yeasts but at higher concentrations there was evidence to suggest that membrane damage accounted for the zymocidal effects of the killer factor. the cidal nature of the toxin was reflected in a rapid decrease in sensitive cell viability. Findings presented suggest that W. mrakii killer toxin has potential as a novel antimycotic agent in combatting medically important strains of Candida.

Antifungal Agents↗

Phylogenetic analysis and rapid identification of Candida dubliniensis based on analysis of ACT1 intron and exon sequences.

The phylogenetic position of Candida dubliniensis has previously been established on the basis of the sequence of rRNA genes. In order to confirm the relationship between C. dubliniensis and other yeast species, particularly Candida albicans, using non-rRNA gene sequences the ACT1 gene was chosen for analysis. Three overlapping fragments that together span the entire C. dubliniensis ACT1 gene (CdACT1) were amplified from a recombinant phage isolated from a genomic DNA lambda library using PCR. These were cloned and used to determine the contiguous sequence of the gene. Analysis of the sequence data revealed the presence of a 1131 bp ORF interrupted by a single 632 bp intron at the 5' extremity of the gene. Comparison of the CdACT1 sequence with the C. albicans homologue (CaACT1) revealed that although the exons are 97.9% identical the introns are only 83.4% identical. Phylogenetic trees generated using ACT1 exon and intron sequences from a range of yeast species unequivocally confirmed the phylogenetic position of C. dubliniensis as a unique taxon within the genus Candida. Analysis of the ACT1-associated intron sequences from 10 epidemiologically unrelated C. dubliniensis isolates from disparate geographical locations showed a very low level of intraspecies sequence variation. In order to develop an accurate and rapid method to identify C. dubliniensis from primary isolation plates the significant divergence between the C. dubliniensis and C. albicans ACT1 intron sequences was exploited by designing C. dubliniensis-specific PCR primers. Using a rapid boiling method to produce template DNA directly from colonies from primary isolation plates in 10 min, these primers were used in a blind test with 122 isolates of C. dubliniensis, 53 isolates of C. albicans, 10 isolates of C. stellatoidea and representative isolates of other clinically relevant Candida and other yeast species. Only the C. dubliniensis isolates yielded the C. dubliniensis-specific 288 bp amplimer. Use of this technique on colonies suspected to be C. dubliniensis allows their correct identification as C. dubliniensis in as little as 4 h.

Actins↗

High-affinity myo-inositol transport in Candida albicans: substrate specificity and pharmacology.

Inositol is considered a growth factor in yeast cells and it plays an important role in Candida as an essential precursor for phospholipomannan, a glycophosphatidylinositol (GPI)-anchored glycolipid on the cell surface of Candida which is involved in the pathogenicity of this opportunistic fungus and which binds to and stimulates human macrophages. In addition, inositol plays an essential role in the phosphatidylinositol signal transduction pathway, which controls many cell cycle events. Here, high-affinity myo-inositol uptake in Candida albicans has been characterized, with an apparent K(m) value of 240 +/- 15 microM, which appears to be active and energy-dependent as revealed by inhibition with azide and protonophores (FCCP, dinitrophenol). Candida myo-inositol transport was sodium-independent but proton-coupled with an apparent K(m) value of 11.0 +/- 1.1 nM for H(+), equal pH 7.96 +/- 0.05, suggesting that the C. albicans myo-inositol-H(+) transporter is fully activated at physiological pH. C. albicans inositol transport was not affected by cytochalasin B, phloretin or phlorizin, an inhibitor of mammalian sodium-dependent inositol transport. Furthermore, myo-inositol transport showed high substrate specificity for inositol and was not significantly affected by hexose or pentose sugars as competitors, despite their structural similarity. Transport kinetics in the presence of eight different inositol isomers as competitors revealed that proton bonds between the C-2, C-3 and C-4 hydroxyl groups of myo-inositol and the transporter protein play a critical role for substrate recognition and binding. It is concluded that C. albicans myo-inositol-H(+) transport differs kinetically and pharmacologically from the human sodium-dependent myo-inositol transport system and constitutes an attractive target for delivery of cytotoxic inositol analogues in this pathogenic fungus.

Azides↗

A model of the pressure dependence of the enantioselectivity of Candida rugosalipase towards (+/-)-menthol.

Transesterification of (+/-)-menthol using propionic acid anhydride and Candida rugosa lipase was performed in chloroform and water at different pressures (1, 10, 50, and 100 bar) to study the pressure dependence of enantioselectivity E. As a result, E significantly decreased with increasing pressure from E = 55 (1 bar) to E = 47 (10 bar), E = 37 (50 bar), and E = 9 (100 bar). To rationalize the experimental findings, molecular dynamics simulations of Candida rugosa lipase were carried out. Analyzing the lipase geometry at 1, 10, 50, and 100 bar revealed a cavity in the Candida rugosa lipase. The cavity leads from a position on the surface distinct from the substrate binding site to the core towards the active site, and is limited by F415 and the catalytic H449. In the crystal structure of the Candida rugosa lipase, this cavity is filled with six water molecules. The number of water molecules in this cavity gradually increased with increasing pressure: six molecules in the simulation at 1 bar, 10 molecules at 10 bar, 12 molecules at 50 bar, and 13 molecules at 100 bar. Likewise, the volume of the cavity progressively increased from about 1864 A(3) in the simulation at 1 bar to 2529 A(3) at 10 bar, 2526 A(3) at 50 bar, and 2617 A(3) at 100 bar. At 100 bar, one water molecule slipped between F415 and H449, displacing the catalytic histidine side chain and thus opening the cavity to form a continuous water channel. The rotation of the side chain leads to a decreased distance between the H449-N epsilon and the (+)-menthyl-oxygen (nonpreferred enantiomer) in the acyl enzyme intermediate, a factor determining the enantioselectivity of the lipase. Although the geometry of the preferred enantiomer is similar in all simulations, the geometry of the nonpreferred enantiomer gets gradually more reactive. This observation correlates with the gradually decreasing enantioselectivity E.

Biotransformation↗

Purification and characterization of secretory proteinase of Candida albicans.

Proteolytic activity of medically important yeasts was tested in both YCB-BSA agar and medium. All of 134 strains of Candida albicans, 13 of 18 strains of Candida tropicalis and 11 of 18 strains of Candida parapsilosis had this activity, while none of 52 Candida glabrata strains or of 11 Cryptococcus neoformans strains tested had proteolytic activity. Strains of C. albicans fell into five groups based on the level and time-course of in vitro proteinase productivity. Five strains randomly selected from each group were tested for pathogenicity in mice. The strain possessing the strongest pathogenicity was used to purify proteinase. The molecular weight of the proteinase was approximately 44,000 daltons and its isoelectric point was pH 4.2. Optimal pH of the proteinase was 3.2 and the enzyme was stable below pH 7.0 and lost its activity above pH 8.0 at 37 C in a 60-min incubation. The 23 amino acid sequence of the proteinase N-terminus was determined.

Amino Acid Sequence↗

Inhibition of Candida albicans growth by murine peritoneal neutrophils and augmentation of the inhibitory activity by bacterial lipopolysaccharide and cytokines.

Anti-Candida activity of murine neutrophils and its regulation by immunomodulators were studied in vitro. Murine neutrophils which were prepared from peritoneal-exudated cells inhibited the growth of Candida albicans at an effector: target (E/T) ratio of 30/1 or above. This anti-Candida activity of neutrophils was augmented by lipopolysaccharide from Escherichia coli, murine tumor necrosis factor (TNF), murine interferon-gamma (IFN-gamma) and murine granulocyte macrophage colony-stimulating factor (GM-CSF) but not by granulocyte colony-stimulating factor (G-CSF) added to the incubation medium. Greater extent of augmentation was obtained when TNF plus GM-CSF or INF-gamma plus GM-CSF were used in combination. These results indicate that anti-Candida activity of murine neutrophils is regulated similarly to that of the human neutrophils reported previously. Therefore murine peritoneal neutrophils can be used as a favorable substitute for human neutrophils in studies on protective machinery against C. albicans infection.

Animals↗

A rapid colorimetric assay for determination of leukocyte-mediated inhibition of mycelial growth of Candida albicans.

A staining method with crystal violet (CV) was demonstrated to be useful for a simple, quick and objective assessment of in vitro growth inhibitory activity of leukocytes against Candida albicans cells. Candida cells incubated with murine neutrophils or macrophages for 14 hr in microwells were stained with CV and, after washing with 0.25% sodium dodecyl sulfate (SDS), treated with isopropanol containing HCl (0.04 N) to extract Candida cell-bound CV. Then the absorbance at 590 nm of the isopropanol extract was photometrically measured. The results showed that the photometrical absorbance was proportional to the amount of 3H-glucose taken up by C. albicans cells, which reflected the number of viable Candida cells.

Animals↗

Biomaterial-associated infection with Candida albicans in mice.

Candida yeasts are frequently isolated from patients with continuous ambulatory peritoneal dialysis peritonitis or other biomaterial-associated infections. The mouse model of candidal peritonitis was used to study the interaction of Candida cells with end-point attached heparinized polyethylene (H-PE) and with polymorphonuclear leukocytes (PMNs) or macrophages (M phi). Two Candida strains differing in cell surface hydrophobicity and in expression of fibronectin (Fn) binding were used for the study. Cells of both Candida strains adhered at higher numbers to H-PE surfaces preadsorbed with Fn or with human dialysis fluid (HDF) than to non-modified H-PE, supporting a role of Fn in mediating adhesion. C. albicans 4016 cells expressing low hydrophobicity and low binding of soluble Fn demonstrated stronger adhesion to PMNs than the more hydrophobic C. albicans 3248 yeasts, which express high binding of soluble Fn. However, C. albicans 4016 cells were more resistant to phagocytic killing and were hardly eradicated in intraperitoneally infected mice. The animals depleted in PMNs by treatment with CY were neither able to eradicate C. albicans 3248 (rapidly eliminated by normal mice) nor C. albicans 4016 yeasts (with a tendency to persist in the tissues of normal mice).

Animals↗

Contact sensitivity to Candida albicans--comparative studies in man and animal (guinea-pig).

We studied the elicitation of contact sensitivity to Candida albicans antigen in guinea-pigs with experimental cutaneous candidiasis and in humans, using commercially available potent 1:100 C. albicans antigen (Torii) by patch testing on abraded skin. In guinea-pigs, non-immune animals became patch test-reactive 4-5 days after topical application of viable C. albicans, either under occlusion or without occlusive dressings, concurrently with the demonstrability of delayed responses to intradermally injected 1:10 000 Candida antigen. In humans, all healthy adults who showed delayed hypersensitivity reactions to intradermally injected 1:10 000 C. albicans antigen demonstrated positive patch-test reactions to 1:100 C. albicans antigen. There was a significant correlation between the magnitude of responses to these tests. In contrast, no positive patch test reactions were elicited to the 1:100 C. albicans antigen on neonatal skin, emphasizing the lack of irritability of this test agent. These results also indicate that in humans contact sensitivity to Candida antigen occurs during later life because C. albicans is a ubiquitous organism. The practical value of this Candida patch test for evaluation of patients' immune function was assessed by a prospective study in patients with various skin disorders. The results obtained suggested some potential value of the test for evaluation of cell-mediated immune function of patients with regard to ubiquitous recall antigens.

Adult↗

Growth and/or acid production of Candida albicans on soft lining materials in vitro.

Effects of soft lining materials on the growth and/or acid production of Candida albicans were investigated using a simplified method monitoring the pH change in the growth medium. Reverse sigmoidal pH curves were observed with all samples and, as compared with acrylic, all soft lining materials inhibited fungal growth or acid production in the following way, i.e. delay of the beginning of a rapid and linear decline in pH, decreases in the rate of linear change in pH and increases in minimum pH. Further examinations using a surface-modified glass tube revealed that the order of Candida growth agreed with the relative hydrophobicity and adherence capacity of substrates, suggesting that this adherence capacity affected the yeast growth on their surfaces. Besides adherence capacities of substrates, the powder, liquid and plasticizer of some soft lining materials directly inhibited Candida growth. Thus, the results obtained here revealed that several factors within soft lining materials affected Candida growth and/or acid production.

Acrylic Resins↗