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Adherence of Candida albicans and Candida dubliniensis to buccal and vaginal cells.

Twenty-seven Candida albicans strains and 26 Candida dubliniensis strains, isolated from HIV patients, were tested for their adherence to buccal and vaginal epithelial cells. Both species showed important levels of adhesion to buccal and vaginal epithelial cells, although C. albicans showed the highest levels of adhesion. These results suggest that both Candida species are well adapted, in terms of adhesion capability, to the oral and vaginal environment.

Candida↗

Protection against systemic infections with various Candida species elicited by vaccination with Candida albicans ribosomes.

This study investigated whether subcutaneous vaccination of mice with ribosomes from Candida albicans strain CBS 562 would also provide protection against infections by other isolates of Candida. Experiments with a total of 628 mice demonstrated that vaccination induced significant protection against heterologous C. albicans (serotypes A and B) and C. tropicalis isolates in terms of their 30 day survival rates. In all instances, however, protection was lower than that obtained against the homologous strain. In addition, a significant decrease in fungal colonization of the kidneys was found in immunized animals as compared to the non immunized controls. Cell-mediated immune responses against cytoplasmic extracts of the various fungi, as detected in vivo by the foot pad swelling test and in vitro by the lymphocyte transformation assay, were induced by the C. albicans ribosomal vaccination. The results show it is possible to induce cross protection to various Candida species by immunization with C. albicans ribosomes.

Animals↗

Relationship between the cell surface hydrophobicity and adherence of Candida krusei and Candida albicans to epithelial and denture acrylic surfaces.

C. krusei is an emerging pathogen, especially in immunocompromised hosts, and is implicated, together with Candida albicans, as an etiological agent of oral candidoses. As the cell surface hydrophobicity of these yeasts appears to be important in the pathogenesis of superficial candidoses, 20 oral isolates of C. krusei and 5 oral isolates of C. albicans were investigated using a biphasic (hydrocarbon/aqueous) separation hydrophobicity assay. All the C. krusei isolates demonstrated significantly greater hydrophobicity than the C. albicans isolates (p < 0.001). Further, there were significant intraspecies differences in cell surface hydrophobicity amongst C. krusei isolates. When hydrophobicity and adhesion to surfaces were compared using data from a previous study, there was a positive correlation between the cell surface hydrophobicity and adhesion of C. krusei isolates to HeLa surfaces (r = 0.53, p < 0.05), but not to acrylic surfaces. The current data, while confirming the inter- and intraspecies differences in cell surface hydrophobicity of Candida species, indicate that this attribute together with other cell surface features may determine the hierarchy of virulence amongst the different Candida species.

Candida↗

[Diagnostic contribution of abnormal delayed-type hypersensitivity to Candida albicans. Characterization test by activation of cells sensitized to successive dilutions of Candida].

By measuring the activation of different cell models (lymphocytes and lymphocytic subsets) in the presence of Candida albicans with flow cytometry reading, it is possible to show that successive dilutions of Candida albicans can lead to lymphocyte activation in abnormally-sensitized subjects. In a first trial, 10 subjects were tested in duplicate. The decrease of activity of the dilutions does not appear to be regular in relation to the progression of the dilutions. The activity of the dilutions wanes relatively rapidly with the first dilutions, then recurs later very distinctly, at the 6th dilution, then ebbs, then reappears in similar manner at the 9th, the 14th, and finally, the 19th dilution. Cell reactivity appears to differ depending on the subject. It can be represented through the calculated slope of the regression line, for each series of data. It therefore appears feasible to determine a threshold of reactivity and a scale of sensitivity, to make it possible to specify the degree of abnormal reactivity existing at a given time for a given subject. The constancy of the activity of the different dilutions tested, on 10 cultures of a single cell suspension, is especially well demonstrated in the second trial, showing unusually small standard deviations. Thus, the question arises as to the exact nature of the observed phenomenon and of its analysis from a physical-chemical point of view, with regard to the pharmacological effect of successive dilutions of Candida albicans.

Adolescent↗

Torulopsis candida (Candida famata) endophthalmitis simulating Propionibacterium acnes syndrome.

Four months after undergoing extracapsular cataract extraction with implantation of a posterior chamber intraocular lens, a 74-year-old woman developed granulomatous anterior uveitis. Although she initially responded well to corticosteroid therapy, she experienced multiple recurrences on discontinuation of this therapy. Slit-lamp examination showed the ocular inflammation to be associated with white cortical material within the lens capsular sac. She underwent removal of the implant as well as the lens capsular sac. Anaerobic culture yielded no organisms, but fungus cultures yielded Torulopsis candida. Histopathologic and electron microscopic studies showed large numbers of yeast sequestered within the lens capsular sac and mild granulomatous inflammation around the sac. Torulopsis candida is occasionally isolated from specimens as a contaminant, but has not yet been shown to produce human disease. The case reported herein documents potential pathogenicity of Torulopsis candida and reveals the importance of organisms other than anaerobic bacteria in causing delayed and localized intraocular inflammation that is virtually identical to Propionibacterium acnes infection.

Aged↗

Systemic candidiasis with candida vasculitis due to Candida kruzei in a patient with acute myeloid leukaemia.

Candida kruzei-related systemic infections are increasing in frequency, particularly in patients receiving prophylaxis with antifungal triazoles. A Caucasian male with newly diagnosed acute myeloid leukaemia (AML M1) developed severe and persistent fever associated with a micropustular eruption scattered over the trunk and limbs during induction chemotherapy. Blood cultures grew Candida kruzei, and biopsies of the skin lesions revealed a candida vasculitis. He responded to high doses of liposomal amphotericin B and was discharged well from hospital.

Acute Disease↗

Rate of transmission and endogenous origin of Candida albicans and Candida glabrata on adult intensive care units studied by pulsed field gel electrophoresis.

We determined the relative roles of endogenous origin and patient-to-patient transmission in Candida colonization of patients on adult intensive care units (ICU). A total of 48 Candida albicans and 18 Candida glabrata strains from various clinical samples of 28 long-term patients, hospitalized in two neurological ICUs between April and June 1999, were typed using pulsed field gel electrophoresis (PFGE). Three patients were co-colonized by both C. albicans and C. glabrata strains. Twenty-four C. albicans and 17 C. glabrata karyotypes were defined. The colonization was found to be polyclonal in six C. albicans and five C. glabrata patients. Twenty-six patients (93%) carried strains, which were not detected in other patients hospitalized at the same time, i.e. they were colonized by unique C. albicans and C. glabrata strains. Only two patients, who were hospitalized during the same period of time, although in different rooms of the same ICU, shared strains with an identical PFGE type, indicating possible patient-to-patient transmission. Patient-to-patient transmission of yeasts played a minor role on these ICUs.

Adolescent↗

Risk factors for nosocomial candiduria due to Candida glabrata and Candida albicans.

The aims of this study were to analyze the clinical characteristics and risk factors associated with catheter-associated candiduria due to Candida glabrata and due to Candida albicans and to compare patients with candiduria due to C. glabrata or C. albicans (cases) with controls. Controls were a randomly chosen sample of inpatients with Foley catheters for whom urine cultures were negative for Candida species. Univariate and multivariate analyses were performed. There were 40 cases of C. glabrata candiduria and 289 cases of C. albicans candiduria. Factors strongly associated with both C. albicans candiduria and C. glabrata candiduria were female gender (P <. 05) and being in the intensive care unit (P <. 01). Fluconazole use (adjusted odds ratio, 4.37; P <. 01) and quinolone use (adjusted odds ratio, 3.16; P <. 01) were specifically associated with C. glabrata candiduria but not with C. albicans candiduria. In conclusion, patients receiving fluconazole treatment are at risk of developing C. glabrata candiduria.

Aged↗

Evaluation of a dehydrated test strip,Microstix -Candida for detection of Candida-induced denture stomatitis.

The outgrowth of yeast from the fitting surface of the maxillary denture and the palatal mucosa was estimated in 63 denture wearers by means of smears and by culture on Microstix-Candida (M-C). There was a significant relationship between the concentration of yeasts as assessed by smears and by M-C. There were confluent spots on M-C, indicating large numbers of yeast cells, in 81% of 37 denture wearers with a positive microscopic diagnosis for Candida-induced denture stomatitis, whereas there were confluent spots on M-C in only one of 26 denture wearers with a negative microscopic diagnosis for infection. It is concluded that the M-C test seems to have sufficient diagnostic sensitivity to be an alternative to the smear for establishing the diagnosis of Candida-induced denture stomatitis.

Candidiasis, Oral↗

The presence of fluconazole-resistant Candida dubliniensis strains among Candida albicans isolates from immunocompromised or otherwise debilitated HIV-negative Turkish patients.

The newly described species Candida dubliniensis phenotipically resembles Candida albicans in many respects and so it could be easily misidentified. The present study aimed at determining the frequency at which this new Candida species was not recognized in the authors' university hospital clinical laboratory and to assess antifungal susceptibility. In this study, six identification methods based on significant phenotypic characteristics each proposed as reliable tests applicable in mycology laboratories for the differentiation of the two species were performed together to assess the clinical strains that were initially identified as C. albicans. Only the isolates which have had the parallel results in all methods were assessed as C. dubliniensis. One hundred and twenty-nine C. albicans strains isolated from deep mycosis suspected patients were further examined. Three of 129 C. albicans (2 from oral cavity, 1 from sputum) were reidentified as C. dubliniensis. One of the strains isolated from oral cavity and that from the sputum were obtained at two months intervals from the same patient with acute myeloid leukemia, while the other oral cavity strain was obtained from a patient who had previously been irradiated for a laryngeal malignancy. Isolates were all susceptible in vitro to amphotericin B, with the MIC range 0.125 to 0.5 &mgr;g/ml, resistant to fluconazole, with MICs >/=64 &mgr;g/ml, and resistant to ketoconazole, with MICs >/=16 &mgr;g/ml, dose-dependent to itraconazole with a MIC range 0.25-0.5 &mgr;g/ml, and susceptible to flucytosine, with a MIC range 1-4 &mgr;g/ml.

Journal Article↗

Inter- and intra-species crosses between Candida albicans and Candida guilliermondii.

Hybridization was shown to occur both between strains of the imperfect diploid yeast Candida albicans and between C. albicans and the distantly related haploid yeast Candida (Pichia) guilliermondii. Prototrophic hybrids were selected from crosses of multiply marked auxotrophic mutants of the two species. In most cases, mild ultraviolet irradiation of the C. albicans partner was required. Examination of auxotrophic markers in segregants from the hybrids indicated that recombination, rather than heterokaryon formation, had occurred in these crosses. The DNA content of the hybrids varied from diploid or aneuploid (for crosses between C. albicans and C. guilliermondii) to triploid (for C. albicans x C. albicans). It seems possible that genetic exchange analogous to this may occur in nature.

Candida↗

Antimicrobial photodynamic therapy mediated by phenothiazine photosensitizers against Candida albicans and Candida auris: a systematic review.

Fungal infections caused by Candida albicans and Candida auris represent an increasing clinical challenge, particularly due to biofilm formation and rising antifungal resistance. Antimicrobial photodynamic therapy (aPDT) has emerged as a potential alternative strategy, with phenothiazine-based photosensitizers being among the most extensively investigated compounds. This systematic review aimed to evaluate the application of phenothiazine-mediated aPDT in in vitro studies against C. albicans and C. auris. A comprehensive search was conducted in PubMed, Embase, and Scopus, including studies published within the last 10 years. Forty in vitro studies met the eligibility criteria and were synthesized descriptively due to substantial methodological heterogeneity. Overall, aPDT was associated with reductions in fungal viability, with generally greater effects reported in planktonic models compared with biofilms. Methylene blue was the most frequently investigated photosensitizer, applied across a broad range of concentrations and dosimetric parameters, resulting in variable antifungal responses. Other phenothiazine derivatives, including toluidine blue O, dimethyl methylene blue, new methylene blue, and S137, were also associated with antifungal activity under specific experimental conditions but remain comparatively underexplored. Studies involving C. auris were less frequent and suggested lower susceptibility compared with C. albicans, particularly in biofilm models. Given the substantial variability in experimental protocols, especially regarding photosensitizer concentration, light parameters, and biofilm maturation, the findings should be interpreted with caution and limit direct comparison across studies. These findings support the antifungal potential of phenothiazine-mediated aPDT while emphasizing the need for methodological standardization and expanded investigation of C. auris.

Photochemotherapy↗

Variations in chromosome size and organization in Candida albicans and Candida stellatoidea.

Candida albicans and the closely related species Candida stellatoidea are medically important diploid asexual yeasts. Clinical isolates frequently show variant electrophoretic karyotypes, apparently due largely to chromosomal translocations. These translocations seem to occur at hot spots characterized by the repeated DNA sequence RSP1. A programmed karyotypic rearrangement occurs in C. stellatoidea. Karyotypic rearrangement may serve as a source of genetic variation in these asexual yeasts.

Candida↗

Effects of voriconazole, granulocyte-macrophage colony-stimulating factor, and interferon gamma on intracellular fluconazole-resistant Candida glabrata and Candida krusei in human monocyte-derived macrophages.

Infections caused by fluconazole-resistant Candida glabrata and Candida krusei are increasingly common causes of morbidity and mortality. We investigated the intracellular killing of fluconazole-resistant C. glabrata and C. krusei by cytokine-activated human monocyte-derived macrophages (MDM) in the presence and absence of voriconazole. For C. glabrata, MDM were activated with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon gamma (IFN-gamma) before infection, after infection, or both before and after infection, whereas for C. krusei MDM were activated with cytokines both before and after infection. Activated MDM were infected, treated with voriconazole, and then lysed, and viable yeast in the lysates enumerated at 0, 24, or 48 h after infection. In the presence of voriconazole (2.5 x MIC), the best activity against C. glabrata occurred when MDM were activated with GM-CSF for 24 h before infection as well as after infection or when they were activated for 24 h before infection alone. A lesser effect was observed when MDM were activated for at least 1 h before infection or when they were treated with cytokines only after infection. IFN-gamma activation had a significant but lesser effect than GM-CSF. Activity against C. krusei in the presence of voriconazole was greatest when MDM were activated with IFN-gamma rather than GM-CSF. Our results suggest that cytokines increase the intracellular anticandidal effect of voriconazole and may be useful as therapeutic adjuvants to voriconazole for treatment of infections caused by fluconazole-resistant C. glabrata and C. krusei.

Antifungal Agents↗

A rapid screening test to distinguish between Candida albicans and Candida dubliniensis using NMR spectroscopy.

Nuclear magnetic resonance (NMR) spectroscopy combined with a statistical classification strategy (SCS) successfully distinguished between Candida albicans and Candida dubliniensis. 96% of the isolates from an independent test set were identified correctly. This proves that this rapid approach is a valuable method for the identification and chemotaxonomic characterisation of closely related taxa. Most discriminatory regions were correlated with metabolite profiles, indicating biochemical differences between the two species.

Candida↗

Molecular responses to changes in the environmental pH are conserved between the fungal pathogens Candida dubliniensis and Candida albicans.

In this work we cloned CdPHR1 and CdPHR2 from the human fungal pathogen Candida dubliniensis. The two genes are homologues to the pH-regulated genes PHR1 and PHR2 from Candida albicans. The pH-dependent pattern of expression of CdPHR1 and CdPHR2 was conserved in C. dubliniensis. CdPHR1 could be shown to be functionally equivalent to PHR1. The pH-regulated mode of expression was maintained when CdPHR1 was integrated in C. albicans. This indicates a fundamentally similar mode of expressional regulation in the two species. CdPHR1 was furthermore capable of reversing the aberrant phenotype of a Saccharomyces cerevisiae GAS1 deletion mutant. In this species, however, expression of CdPHR1 was no longer under control of the external pH. Expression of CdPHR1 was not detected when it was introduced into Aspergillus nidulans. In conclusion, C. dubliniensis and C. albicans respond to changes in the environmental pH with a change in cell shape and differential gene expression.

Apoenzymes↗

Microevolutionary changes and chromosomal translocations are more frequent at RPS loci in Candida dubliniensis than in Candida albicans.

The Cd1 fingerprinting probe of Candida dubliniensis, which is extremely effective in identifying microevolutionary changes in infecting populations, generates hybridization patterns that are similar to those generated by the Candida albicans fingerprinting probe Ca3. Since Ca3 recognizes microevolutionary changes through the repeat sequence RPS, it was suggested that Cd1 also contains a RPS-like element. To test this possibility, the C. albicans RPS unit was used as a probe, and an RPS-like element, RPSd1, was cloned from C. dubliniensis. The sequence of RPSd1 was 76% homologous to that of the C. albicans RPS unit RPS620 and the organization, including the non-RPS 3' and 5' bordering sequences, was highly similar. This analysis revealed additional copies of the repeat extraalt element and short additional repeat (SAR) sequences in both RPSd1 and RPS620 not previously identified in the latter. This analysis has allowed us to develop a model of RPSd1 organization and to revise the model for RPS620 organization. An estimate of the average frequency of reorganization (duplication and deletion) per RPS unit in C. dubliniensis was similar to that for C. albicans, but the estimate of frequency of reorganization per C. dubliniensis genome was higher, most probably as a result of the higher estimated average number of RPS clusters in C. dubliniensis. These results demonstrate that the microevolutionary changes identified by the Cd1 fingerprinting probe are based on the reorganization of RPS-like elements and are, therefore, similar to the microevolutionary changes identified by the Ca3 probe of C. albicans. Linkage analysis of pairs of markers situated on either side of an RPS cluster on chromosome 7 further revealed frequent recombination between non-homologous chromosomes at the RPS cluster in C. dubliniensis strains, but not in C. albicans strains, suggesting that RPS clusters may function as recombination hot spots in C. dubliniensis.

Base Sequence↗

Comparison of the epidemiology, drug resistance mechanisms, and virulence of Candida dubliniensis and Candida albicans.

Candida dubliniensis is a pathogenic yeast species that was first identified as a distinct taxon in 1995. Epidemiological studies have shown that C. dubliniensis is prevalent throughout the world and that it is primarily associated with oral carriage and oropharyngeal infections in human immunodeficiency virus (HIV)-infected and acquired immune deficiency syndrome (AIDS) patients. However, unlike Candida albicans, C. dubliniensis is rarely found in the oral microflora of normal healthy individuals and is responsible for as few as 2% of cases of candidemia (compared to approximately 65% for C. albicans). The vast majority of C. dubliniensis isolates identified to date are susceptible to all of the commonly used antifungal agents, however, reduced susceptibility to azole drugs has been observed in clinical isolates and can be readily induced in vitro. The primary mechanism of fluconazole resistance in C. dubliniensis has been shown to be overexpression of the major facilitator efflux pump Mdr1p. It has also been observed that a large number of C. dubliniensis strains express a non-functional truncated form of Cdr1p, and it has been demonstrated that this protein does not play a significant role in fluconazole resistance in the majority of strains examined to date. Data from a limited number of infection models reflect findings from epidemiological studies and suggest that C. dubliniensis is less pathogenic than C. albicans. The reasons for the reduced virulence of C. dubliniensis are not clear as it has been shown that the two species express a similar range of virulence factors. However, although C. dubliniensis produces hyphae, it appears that the conditions and dynamics of induction may differ from those in C. albicans. In addition, C. dubliniensis is less tolerant of environmental stresses such as elevated temperature and NaCl and H(2)O(2) concentration, suggesting that C. albicans may have a competitive advantage when colonising and causing infection in the human body. It is our hypothesis that a genomic comparison between these two closely-related species will help to identify virulence factors responsible for the far greater virulence of C. albicans and possibly identify factors that are specifically implicated in either superficial or systemic candidal infections.

Antifungal Agents↗