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PubMed2003

Phagocytosis of candida albicans by lymphatic tumour cells in vitro.

Experiments were carried out to investigate whether different lymphatic tumour cell lines have similar kinetic characteristics of phagocytosis of microorganisms. Six tumour cell lines were used. These were a human T-cell line (CEM), a mouse T-cell line (YAC-1), a human B-cell line (LAZ), and a human erythroleukemic tumour cells (K562), whereas 2 cell lines of professional phagocytosis were used as controls, a human macrophage cell line (THP1) and a mouse macrophage cell line (P388D1). Tumour cells were mixed with candida albicans at a ratio of 10:1 of candida to tumour cells and the percentage of tumour cells that had attached/phagocytosed candida was determined. After 4 h coculture with candida, tumour cells not of T-cell origin (LAZ and K562) showed moderate level of phagocytosis (28%), whereas tumour cells of T-cell origin (CEM and YAC-1) demonstrated low levels of phagocytosis (15%) as compared to macrophage cell lines (THP1 and P388D1) that showed maximum phagocytosis (64-78%). Acid phosphatase (AcPase) activity was increased by 33% during coculture of YAC-1 cells and yeast cells. In conclusion, the results suggest that lymphatic tumour cells of nonphagocytic origin acquire phagocytic properties during the course of malignancy, and digestion of phagocytosed yeast cells maybe related with AcPase activity, as well as that of other lysosomal enzymes. This phenomenon may represent one mechanism by which tumour cells downregulate immune surveillance.

Acid Phosphatase↗
PubMed2003

Importance of the terminal complement components for immune defence against Candida.

Candida activates complement via all three pathways leading to opsonisation and anaphylaxis. The aim of the study was to investigate the influence of the terminal complement system on Candida infections. Thus, fungal cell growth, mitochondrial activity and phagocytosis by polymorphonuclear leukocytes (PMNLs) as well as specific virulence factors, such as release of secreted aspartic protease (Sap) and adherence to epithelial cells, were assessed under the influence of normal or C6/C7-depleted serum. Candida (C.) dubliniensis was used in all experiments as prototype because of its known increased expression of Saps and its strong geno- and phenotypical similarity to the most abundant Candida species C. albicans. Being exposed to sufficient quantities of complement, fungal growth decreased and phagocytosis increased but mitochondrial activities of the yeast increased as well. Concerning the virulence factors, both adhesion and especially Sap release were markedly reduced in the presence of high serum concentrations. Interestingly, at low serum concentrations some opposite effects (an augmented cell growth, a higher Sap release and a stronger adhesion) were observed. In particular, it was shown that the presence of terminal complement factors, and thus the generation of the membrane attack complex, clearly induced a higher fungal mitochondrial activation and has an effect on host defence against yeast cells by augmenting phagocytosis.

Candida↗
PubMed1984

A comparison of experimental pathogenicity of Candida species in cyclophosphamide-immunodepressed mice.

The experimental pathogenicity of Candida albicans, C. krusei, C. guilliermondii, C. parapsilosis, C. tropicalis and C. viswanathii was tested in normal and in cyclophosphamide-(Cy) immunodepressed mice. In unpretreated CD1 mice only C. albicans, C. tropicalis and C. viswanathii were pathogenic on intravenous challenge, with LD50 of 1.0 X 10(6), 4.8 X 10(6), 7.2 X 10(8) cells, respectively, per kg. Three days after a single intraperitoneal injection of Cy (150 mg kg-1) mice had a marked decrease in spleen weight and cellularity as well as reduced numbers of circulating leukocytes. Under these conditions, there was a significant, proportional increase in pathogenicity of C. albicans, C. tropicalis and C. viswanathii but the animals were still resistant to challenge with C. krusei, C. guilliermondii and C. parapsilosis. This pattern of susceptibility was not influenced by higher doses of Cy. Only C. albicans and C. tropicalis were capable of rapid and extensive multiplication in target organs such as kidney and brain in normal and Cy-treated mice and for both these species of Candida, there was a 'rebound' effect of increased resistance to experimental infection after 12 days from Cy administration. This study shows that the strong immunodepression provoked by Cy does not modify significantly the susceptibility of the animal to those species of Candida which were endowed with low or no pathogenicity for normal mice, but it greatly increases the susceptibility to those species of Candida that are already pathogenic for unmodified host.

Animals↗
PubMed2002

Constrictive pericarditis caused by candida glabrata in an immunocompetent patient: case report and review of literature.

Candida pericarditis is a rare disease described mostly in patients with recent cardiothoracic surgery or debilitating chronic diseases and is generally considered to be associated with high mortality. To our knowledge, we report the first case of Candida pericarditis in a healthy host who had not undergone thoracic surgery and the first documented case and cure of pericarditis caused by C. glabrata. The most probable underlying factor in the development of this pericarditis was the abdominal surgery the patient underwent to correct a gastrogastric fistula, without an intraabdominal leak, which developed 10 y after surgical gastric stapling for weight reduction. The literature on Candida pericarditis is reviewed. If Candida pericarditis is diagnosed early and treated with a combined medical and surgical approach, the prognosis today is much more favorable than that previously reported.

Adult↗
PubMed2004

Clinical significance of untreated Candida species isolated from ascites in cirrhotic patients.

The clinical significance of Candida species isolated from cirrhotic ascites is still unknown. We reviewed the clinical and laboratory features of all cirrhotic patients whose ascites samples were positive for Candida species. A total of 21 cirrhotic patients was identified. Patients were regarded as having peritonitis if they had 1 or more clinical symptom(s) or sign(s) in the absence of any other possible explanation. 10 patients (47.6%) were classified into the spontaneous Candida peritonitis (SCP) group, and the remaining 11 patients (52.4%) were classified into asymptomatic candidascites. Mortalities were higher in the SCP group at discharge (50.0% vs 27.3%), 6-month (90% vs 45.5%) and 1-y (100% vs 54.5%) (p=0.007). Receiver-operating characteristic curve analysis revealed that the cut-off value of ascitic fluid polymorphonuclear cell count of 315/mm(3) (0.315 x 10(9)/l) had the highest diagnostic accuracy with both sensitivity and specificity of 1.0. In conclusion, Candida species are associated with a grave outcome when manifested with peritonitis.

Adult↗
PubMed1988

Candida concentrations in the vagina and their association with signs and symptoms of vaginal candidosis.

Among 106 women harbouring yeasts in the vagina and with other causes of genital pathology excluded, there was a statistically significant association between numbers of yeasts recovered semi-quantitatively from vaginal swabs and symptoms of pruritus and signs of abnormal vaginal discharge but no association between yeast numbers and other individual symptoms or signs of vaginal candidosis, including patients' own subjective assessment of abnormal vaginal discharge. The presence of yeasts detectable by direct microscopic examination was statistically associated with pruritus, discharge and vaginitis. There was no relationship between numbers of vaginal yeasts and histories of antibiotic or oral contraceptive usage or the stage of the menstrual cycle. Distributions of Candida species and Candida albicans biotypes were not statistically related to any symptoms, signs or other factors. The results of this study suggest that vaginal pathology caused by Candida species may be related to the quantity of the fungus in the vagina and that only pruritus and objectively assessed vaginal discharge are firm clinical indicators of Candida infection.

Candida↗
PubMed1991

Biochemical and antigenic characterization of mannoprotein constituents released from yeast and mycelial forms of Candida albicans.

Yeast or mycelial cultures of Candida albicans released comparable amounts of Concanavalin A-reactive mannoprotein material after 24-h of growth, and in both cases this material showed a qualitatively similar SDS-PAGE pattern, with predominantly polydisperse constituents of high molecular mass. The two secretion mixtures also showed similar reactivity by ELISA with serum from a subject with high titre anti-Candida antibodies, as well as with an anti-Candida hyperimmune antiserum raised in rabbits. Both secreted extracts were separated by ion-exchange chromatography into two major fractions (designated F1 and F2), each containing mannoprotein antigens recognized by rabbit and human sera, although the immunoreactivity of the two fractions from the two growth forms was not uniform. The mannoproteins released from mycelial cultures, in particular those present in the F1 fraction, were poorly reactive or not reactive at all in ELISA with a monoclonal antibody (mAbAF1) which strongly recognized the material released from yeast cultures. Immunoblots of the more acidic, more antigenic F2 fractions with mAbAF1 and polyclonal anti-Candida antisera demonstrated that the monoclonal antibody did not recognize several mannoprotein molecules which were recognized by the polyclonal antibodies, in particular a 45-47 kDa component present only in the secreted extract from mycelium. A quantitative ELISA-inhibition method showed that the rate of release of mannoprotein antigen during growth in the yeast form was either constant (as assayed with polyclonal antibodies) or fluctuated without any definite trend (as seen with mAbAF1). On the other hand, cultures of mycelial cells exhibited an early (90 min) peak of antigen release, followed by either a decrease to a rate corresponding to that of yeast cells (with polyclonal antibodies) or a total lack of secretion (with mAbAF1). This modulation in the secretion of mAbAF1 reactive molecules was temporarily associated with germ tube emergence-elongation, and was not observed in an agerminative mutant of C. albicans grown under germination permissive conditions. These results highlight the dynamic aspects of the secretion of specific mannoprotein epitopes released from C. albicans during hyphal growth, and the direct relationship between this release and the dynamic expression of the same epitopes on the cell surface demonstrated previously.

Antigens, Fungal↗
PubMed1992

Stimulation of Candida albicans transition by human chorionic gonadotrophin and a bacterial protein.

Candida albicans, a dimorphic fungus, is involved commonly in human infections with the mycelium form more associated with pathogenicity. The influence of various hormones and a bacterial protein on the transition from blastospore to mycelium was assessed. Human luteinizing hormone (hLH), chorionic gonadotrophin (hCG), and an hCG-like material purified from a bacteria, Xanthomonas maltophilia (PCG), were able to increase the rate of transition when compared with the controls. The effect of the two hormones and the bacterial peptide were specific, as human follicle stimulating hormone (hFSH), thyroid stimulating hormone (hTSH), growth hormone (hGH), prolactin (hPrl) and rat and bovine LH (rLH, bLH), and bovine albumin and gamma globulin did not affect the transition. The binding of 125I-hCG or 125I-LH to spheroplasts of Candida albicans were competitively displaced by hCG, hLH, and PCG. Scatchard analysis of binding of all three ligands revealed two binding sites with a high-affinity nM Kd. Thus, hCG, hLH, and PCG induce transition of Candida albicans from a blastospore state to a mycelium form, suggesting that these hormones may modify the pathogenicity of Candida albicans.

Bacterial Proteins↗
PubMed2005

Detection of Candida species in vaginal samples in a clinical laboratory setting.

OBJECTIVE: To present the detection rates of Candida species in vaginal samples from patients visiting physicians. METHODS: The presence of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis in 3978 vaginal swabs from patients in six US states was detected by PCR amplification. RESULTS: Candida DNA was detected in 33.1% of the population studied. Of the 1316 positive samples, 80.2% contained C. albicans, 14.3% contained C. glabrata, 5.9% contained C. parapsilosis and 8.0% contained C. tropicalis. Comparing samples by patients' state of residence revealed an association with the detection of C. glabrata (p = 0.029). Comparing samples by patients' age revealed a decrease in the overall detection of Candida (p < 0.001) and C. albicans (p < 0.001), concomitant with an increase in the detection of C. glabrata (p < 0.001) and C. parapsilosis (p = 0.025). CONCLUSIONS: These results provide geographic- and age-specific data on four Candida species associated with vaginitis.

Adolescent↗
PubMed2005

In vitro activity of caspofungin compared to amphotericin B, fluconazole, and itraconazole against Candida strains isolated in a Turkish University Hospital.

We investigated the in vitro activity of caspofungin compared to amphotericin B, fluconazole, and itraconazole against clinical strains of Candida spp. (n =239). Antifungal susceptibility tests were done in accordance with NCCLS M27-A2 microdilution method and the results were read after 24 and 48 h. In general, 24 h MIC readings were similar to those at 48 h for most isolates and all antifungal agents. Caspofungin was active against all species tested. Caspofungin MICs of Candida parapsilosis were slightly higher than those for other Candida spp. Caspofungin MIC (microg/ml) ranges at 24 h for C. albicans, C. glabrata, C tropicalis, C. parapsilosis, C kefyr, C krusei, C. lusitaniae, C. norvegensis, C. guilliermondii and C. lipolytica were 0.06-2, 0.125-2, 0.125-2, 1-4, 0.125-2, 1-2, 0.5-2, 0.5-1, 0.5-2 and 1-2, respectively. Eagle (paradoxical) effect was observed in 31 and 8% of the isolates at highest concentrations of caspofungin and itraconazole, respectively. The activity of caspofungin against fluconazole- and/or itraconazole-resistant isolates was similar to that detected for the susceptible ones. We conclude that caspofungin appears as a promising antifungal agent with enhanced activity against Candida, including the azole-resistant strains.

Amphotericin B↗
PubMed2005

Immunotherapeutic approaches to enhance protective immunity against Candida vaginitis.

Protective host defense mechanisms against vaginal Candida infections are poorly understood. While cell-mediated immunity (CMI) is the predominant host-defense mechanism against most mucosal Candida infections, no protective role for systemic or local Candida-specific CMI or antibodies has been identified against vaginal candidiasis. Rather, evidence exists for immunoregulation in vaginal tissue, which may inhibit a more profound protective Th1-type response. This study evaluated immunotherapy and gene therapy approaches in the murine model to potentially overcome immunoregulation and promote enhanced protection against vaginal candidiasis. In the first set of studies, the intravaginal and systemic administration of Thl-type cytokines and anti-IL-10 and anti-TGF-beta antibodies failed to enhance protection against a vaginal Candida infection. In a second set of studies, the novel intravaginal administration of Adenoviruses encoding Th1-type cytokines (IFN-gamma and IL-12) and the chemokine, MCP-1, showed substantial, but transient (24 h) expression of each in vaginal tissue and draining lymph nodes, even with a second administration. Unfortunately, treatment with these Adenoviral vectors did not enhance protection against experimental vaginitis. Construction of a new vector encoding IFN-gamma with a stronger promoter produced substantial IFN-gamma in vitro, but lower amounts in vivo and no extended expression. Taken together, while gene therapy can be used to induce cytokine expression in vaginal tissue, there appear to be strong regulatory mechanisms that additional manipulations or alternative approaches will have to overcome if protection against vaginitis is to be enhanced.

Animals↗
PubMed2006

Effects of vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin, and telithromycin on murine gut colonization by Candida albicans.

Crl:CDI(ICR) BR adult mice were fed chow containing Candida albicans or regular chow. Both groups were subsequently given either antibiotics acting mainly against Gram-positive organisms or normal saline for 10 days. Stool cultures were performed before, at the end, and one week after discontinuation of treatment to determine the effects on the stool yeast concentration. Candida colonized mice treated with vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin or telithromycin had higher colony counts of yeast in their stools than control Candida fed mice treated with saline. This increase was not statistically significant. Mice fed regular chow treated with the study drugs or saline did not have any yeasts in their stools. Dissemination of Candida was not observed in the visceral organs of any mouse.

Animals↗
PubMed2006

Biofilm production by clinical isolates of Candida species.

Candida species are a leading cause of infections especially in immunocompromised hosts. Usage of bio-prostheses such as IV lines and urinary catheters provide ample opportunity for Candida biofilms to set up a nidus for disease that is not easily amenable to conventional antifungal therapy. To understand the prevalence of biofilm producers among clinical isolates, 58 Candida isolates from immunocompromised patients were examined. Thirty of the 36 (83.3%) blood stream' isolates and 18 of the 22 (81.8%) oral isolates were biofilm producers. Biofilm producing blood stream isolates were significantly more among non-C. albicans Candida (93.1%) in comparison to C. albicans (42.9%).

Biofilms↗
PubMed2006

Comparative effects of ertapenem, imipenem, and meropenem on the colonization of the gastrointestinal tract of mice by Candida albicans.

We evaluated the effect of three carbapenems on gut colonization of mice by Candida albicans. A total of 150 Crl:CD1 (ICR) BR mice were fed chow containing C. albicans or regular chow. Both groups were subsequently treated either with one carbapenem or with normal saline for 10 days. Stool cultures to determine colonization by C. albicans were performed immediately before, at the end, and one week after the end of treatment. Candida-colonized mice that received carbapenems had substantially higher C. albicans concentrations than control animals fed C. albicans, especially if they received ertapenem. Mice fed regular chow and treated with the study antibiotics or saline did not have Candida in their stools. Candida was not detected in the internal organs of any group of mice.

Animals↗
PubMed2003

Amplification-based nucleic acid scanning techniques to assess genetic polymorphism in Candida.

Opportunistic pathogen Candida causes common fungal infections that manifest both superficially and systemically, especially in compromised patients. Although C. albicans is by far the main etiological agent of candidosis, the frequency of isolation of other non-albicans species such as C. glabrata and C. krusei is increasing at an alarming rate. Therefore, the epidemiology, pathogenicity, and diagnosis of infections due to these organisms are of great importance. Of a variety of genotyping methods utilized for strain delineation of these Candida species, amplification-based techniques such as randomly amplified polymorphic DNA (RAPD), amplified fragment length polymorphism (AFLP), restriction digestion-mediated PCR (RFLP-PCR), and single-stranded conformational polymorphism (SSCP) and microsatellite PCR (interrepeat PCR, IR-PCR) are the most popular and widely used. In the last decade or so these techniques have helped unravel the clinical epidemiological features of pathogenicity, diversity, microevolution, and natural heterozygosity in Candida species. Here we review in detail the basic principles of RAPD, the nature of the primer and factors influencing its selection, and the limitations of RAPD assays as well as analysis and interpretation of banding profiles generated using the software programs. In addition, the principles of other RAPD-based amplification techniques (AFLP, RFLP-PCR, SSCP, and IR-PCR) and their application in molecular epidemiologic studies of Candida species in particular and other fungi in general are also reviewed. It is concluded that these methods have wide applicability in genotyping fungi, although they differ greatly in their resolution and have advantages and drawbacks depending on the task in question.

Candida↗
PubMed2002

Fungicidal activities of commonly used disinfectants and antifungal pharmaceutical spray preparations against clinical strains of Aspergillus and Candida species.

The antifungal efficacy of commercial chemical disinfectants and pharmaceutical antifungal agents against medically important moulds and yeast species was investigated. Chlorine, phenol, sodium dodecyl sulfate and quaternary ammonium salts were the chemical disinfectants, and bifonazole and terbinafine were the antifungal pharmaceutical products tested against clinical isolates of Aspergillus and Candida species. Fungal inocula were obtained from conidial preparations of two A. ochraceus strains and yeast cells of C. albicans, C. krusei and C. parapsilosis. The antifungal activities were evaluated either by determining the kill rate in a cell suspension media at different contact periods, or by examining the viability and growth on plates sprayed with the active ingredient. Chlorine (1%) was the only disinfectant with the ability to cause a rapid inactivation of all five strains. Phenol (5%) was equally effective against Candida species; however, a number of A. ochraceus conidia were able to survive this treatment for up to 1 h. Benzalkonium chloride (0.5%) and cetrimide (0.5%) were also able to disinfect the three Candida species rapidly; however, these two quaternary ammonium compounds were relatively ineffective against A. ochraceus. In spray experiments, quaternary ammonium compounds had a fungicidal activity against Candida species and were fungistatic against A. ochraceus conidia. All five fungal strains were able to resist 0.5% sodium dodecyl sulfate, present either in the suspension solution or on the sprayed plate. Of the two pharmaceutical antifungal products tested, bifonazole (1%) were essentially ineffective against all five strains. Terbinafine (1%) had a fungicidal activity against A. ochraceus and C. parapsilosis. In suspension experiments, an exposure to 0.01% terbinafine required a contact period of 1 h for a complete inactivation of A. ochraceus conidia and an onset of fungicidal effect on C. parapsilosis yeast cells. Terbinafine was only moderately effective against C. albicans and was completely ineffective against C. krusei.

Antifungal Agents↗