We investigated a fluconazole-sensitive (MICflu = 5 micrograms ml-1) clinical isolate and a fluconazole-resistant (MICflu > 80 micrograms ml-1) laboratory mutant Candida albicans strain developed from the sensitive one. We studied putative virulence factors including germination, adherence ability to either buccal epithelial cells or acrylate surface, the secreted aspartic proteinase, and the extracellular phospholipase activity of the two strains as well as their growth. The fluconazole-resistant strain proved to be superior to the original strain in all the virulence traits tested. The higher virulence of the fluconazole-resistant strain was also supported by a mouse model. These results suggest that the development of fluconazole resistance can be accompanied by serious morphological and physiological changes: several putative virulence traits, moreover the in vivo virulence can increase simultaneously.
The effect of fluconazole and the antineoplastic agents etoposide and methotrexate on the growth and adhesion of Candida albicans were studied. All the tested chemicals inhibited the growth and the adhesion of the yeast to buccal epithelial cells, while fluconazole and etoposide inhibited the adhesion to acrylate surface as well. Our experiments also demonstrated that etoposide and methotrexate interfered with the inhibitory effect of fluconazole on both the growth and cell adhesion. While etoposide strengthened the inhibitory effect of fluconazole, in the presence of methotrexate fluconazole showed lower inhibition on both the growth and adhesion.
Hyphal growth of Candida albicans was observed when yeast was cultured at 27 degrees C in liquid media containing 1% Tripcasine and 1.8% cyclodextrins (alpha, beta, and gamma respectively). Tripcasine as the sole nitrogen source did not induce the formation of hyphae of C. albicans, but cyclodextrins, especially CD-beta, were able to induce yeast-mycelial transition. In the TCD-beta media 25-30% septate hyphae form was observed. This study indicates the existence of an uptake system for CDs in C. albicans, provided these compounds are linearised in the medium. The CDs are inducers of hyphae and they may enter the C. albicans cells as linear oligosaccharids.
In this study, the a-glucosidase of C. albicans as a potential virulence factor was investigated. We compared the intracellular and intact-cellular activities of two C. albicans strains: a clinical isolate (FS) and a laboratory mutant (FR) derived from the former. Although the FR strain was superior in all the virulence factors examined as well as in its in vivo virulence, similar intact-cellular a-glucosidase activities were obtained for the two strains. Moreover, the intracellular a-glucosidase activity of the FR strain was lower than that of the FS strain. Making a survey on 20 clinical isolates of C. albicans, the D-glucosidase activities did not correlate with either the extracellular aspartic proteinase (EAP) or the extracellular phospholipase (EP) activities, although we found a correlation between the EAP and EP activities. In conclusion, our experiments do not support the view that the inducible a-glucosidase is a virulence factor of C. albicans.Candida albicans is the leading micro-organism causing invasive fungal diseases in hosts with human immunodeficiency virus infection or with other immunosuppressed conditions. Despite of appropriate therapies, the mortality rate of systemic C. albicans infections in immunocompromised patients approaches 30% (WENZEL and PFALLER 1991). Several factors are known to contribute to the pathogenicity of C. albicans. These include dimorphic transition, the ability to switch between different cell phenotypes, adhesion to inert and biological substrates, and the secretion of hydrolytic enzymes (KWON-CHUNG et al. 1985, CUTLER 1991, IBRAHIM et al. 1995.C. albicans is able to induce disaccharide-degrading enzymes under carbohydrate restriction conditions. The production of such hydrolases may enable the fungus to grow in the host tissues even when the carbohydrate supplementation is restricted. Therefore, the inducible a-glucosidase is usually considered as a potential virulence factor of C. albicans (WICKES et al. 1991, BRAMONO et al. 1995) but this opinion is not generally accepted. For example, KWON-CHUNG et al. (1990) reported that there was no significant difference in virulence between strains which did or did not assimilate sucrose.In this study, we determined the intracellular and intact-cellular a-glucosidase activity of two C. albicans strains which differed markedly in all the examined putative virulence traits as well as in their in vivo virulence (FEKETE-FORGÁCS et al. 2000). We also measured the a-glucosidase activities in 20 clinical isolates of C. albicans, and the possible correlations with the extracellular aspartic proteinase (EAP) and the extracellular phospholipase (EP) activities of these strains were also investigated. Materials and methodsChemicals: SABOURAUD dextrose agar (SDA) and mycological peptone were purchased from OXOID (Basingstoke, Hampshire, England). Yeast carbon base (YCB) and sterile egg yolk enrichment were obtained from DIFCO Laboratories (Detroit, Michigan, USA) while p-nitrophenyl-a-D-glucopyrano-
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