44 research outputs found
Emerging strategies for environmental decontamination of the nosocomial fungal pathogen Candida auris
Atividade antifúngica do extrato aquoso de Arctium minus (Hill) Bernh. (Asteraceae) sobre espécies orais de Candida
Factors affecting the adherence of Candida albicans to human buccal epithelial cells in human immunodeficiency virus infection
Adherence to host surfaces is an essential prerequisite for colonization and infection. We compared the adherence of 15 oral isolates of Candida albicans harvested from human immunodeficiency virus (HIV)-infected individuals and 12 isolates from HIV-free individuals to buccal epithelial cells (BECs) from HIV-free individuals, and the adherence of a reference strain of C. albicans to BECs from HIV-infected as well as HIV-free individuals. C. albicans from HIV-infected individuals showed adherence values similar to those from HIV-free individuals. The clinical and laboratory parameters of the subjects from whom the Candida were isolated did not correlate with adherence. A reference strain of C. albicans (GDH 1957), however, adhered more readily to BECs from HIV-infected individuals than to cells from an HIV-free cohort. Several variables were found to be associated with the adherence of C. albicans to BECs from HIV-infected individuals: use of zidovudine, antibacterials and antiparasitics was associated with increased adhesion, while haemophilia, heterosexuality, bisexuality, increased age, decreased CD4 + count and use of folate were associated with a decreased candidal adhesion (all P < 0.05). Our data suggest that the quality of BECs including their receptivity to Candida may play an important part in increasing the oral yeast carriage in HIV infection.link_to_subscribed_fulltex
Heterogeneity in antifungal susceptibility of clones of Candida albicans isolated on single and sequential visits from a HIV-infected southern Chinese cohort
The increased frequency and severity of candidal infections in human immunodeficiency virus (HIV)-infected individuals has prompted the wide use of antifungals, such as amphotericin B, ketoconazole, and fluconazole, resulting in the emergence of drug-resistant strains of Candida albicans. To study this phenomenon in an ethnic Chinese cohort, we isolated multiple colonies of Candida from the oral cavities of 16 HIV-infected patients on single and subsequent sequential visits over a period of 12 months. Ten of the 16 patients had sporadic episodes of oropharyngeal candidiasis (Group A), while the remainder were asymptomatic with respect to this condition (Group B). Oral rinses were collected and immediately processed in the laboratory for the isolation of C. albicans in a standard manner. A total of 433 C. albicans isolates were tested for their susceptibility to amphotericin B, ketoconazole and fluconazole by an agar diffusion method using the commercially available E-test. All tested isolates demonstrated variable susceptibility to amphotericin B, ketoconazole and fluconazole. The minimum inhibitory concentration (MIC) of the isolates for amphotericin B, ketoconazole and fluconazole ranged from <0.002-1.5 μg/ml, <0.002-4.0 μg/ml and <0.016-32 μg/ml, respectively. Sequential isolates of a few patients demonstrated variable susceptibility to all the antifungals, and no discernible MIC pattern emerged either in group A or B over time. Interestingly, significant variation in antifungal susceptibility was also noted in isolates obtained from the same patient on a single visit. Sequential yeast isolates in 9 of 16 patients (56%) demonstrated significant differences in MIC within and between visits for both amphotericin B and ketoconazole, while a lower percentage - 44% (7/16) - exhibited this trait for fluconazole. Our study demonstrates the diversity in antifungal susceptibility in either commensal or "infective" oral strains of C. albicans in HIV disease, and shows the need for vigilance for the emergence of resistant strains, and for frequent antifungal susceptibility studies.link_to_subscribed_fulltex
Investigation of the functional significance of phytase activity in human fungal pathogen Candida albicans
Introduction and Project Objectives: Candida albicans is one of the most prevalent human fungal pathogens. In healthy individuals, C. albicans cohabits as a harmless commensal on the skin and mucosal surfaces of oral cavity, digestive tract and urogenital system. In cases of impaired immunity, C. albicans can become invasive and cause an infection (candidiasis). Mild superficial infection is not fatal, but disseminated candidiasis can be life-threatening. The ability of pathogens to colonize and proliferate in host tissues contributes to pathogenicity. Phosphorus is a building block of nucleic acids, ATP and is involved in phosphorylation and glycolysis. Myo-inositol plays key role in membrane formation, signal transduction and osmoregulation. More importantly, it is a precursor of cell surface glycosylphosphatidylinositol-anchored glycolipids, a C. albicans virulence trait through interactions with human macrophages. Phytate degradation by phytase liberates myo-inositol and inorganic phosphate, both are essential molecules for fungal growth and pathobiology. Our previous study demonstrated the presence of phytase activity in Candida fungi and suggested its potential involvement in host-pathogen interactions. The objectives of this study were: (1) To create C. albicans phytase null mutants and examine their phenotypic determinants; (2) To examine the effects of pH and transcription factors on phytase activity; and (3) To evaluate the importance of phytase activity in C. albicans fitness and virulence. Methods: C. albicans phytase null mutants were created using a PCR-based gene targeting method. The phenotypic properties of the mutants were evaluated, including phytase activity, fungal growth, yeast-to-hyphal morphogenesis, adhesion to buccal epithelial cells (BECs), and virulence. The effect of pH on phytase activity was evaluated by incubating the fungal cells at different pH (from 4.0 to pH 8.5). The effect of transcription factors on phytase activity was investigated using quantitative PCR. Results: C. albicans phytase null mutants have been created and verified. Biochemical analyses indicated that PHO112 contributed to the C. albicans phytase activity. C. albicans pho112Δ/pho112Δ possessed decreased phytase activity, reduced ability to form hyphae in the presence of fetal calf serum at 37oC, and attenuated adhesion to BECs and virulence. pH and transcription factors had no effect on phytase activity. Conclusions: The collective data of the present study suggest that PHO112 is responsible for the C. albicans phytase activity, which is not affected by pH and transcription factors; and virulence
Deletion of Candida albicans PHO112 reduces phytase activity, hyphal development, and attenuates virulence
Objective: To investigate the functional roles of PHO112 in Candida albicans phytase activity, hyphal development, and virulence. Methods: C. albicans PHO112 null mutants were created by a PCR-based gene targeting method using gene-specific primers. C. albicans PHO112 reintegrants were created by transforming the full length PHO112 gene into the C. albicans PHO112 null mutants. Phytase activity in C. albicans PHO112 null mutants was determined by quantifying the amount of released inorganic phosphate from sodium phytate using ammonium molybdate. The ability to form hyphae was evaluated in YPD medium supplemented with 10% fetal bovine serum at 37oC (hyphal-inducing conditions). Adhesion to buccal epithelial cells (BECs) was evaluated by counting the number of attached fungal cells to Gram’s stained BECs under light microscope. Fungal pathogenicity was determined using reconstituted oral human epithelial (ROHE) tissues, and histological changes of the tissues were observed under light microscope after staining with hematoxylin and eosin. Results: C. albicans PHO112 null mutants were created and verified by PCR and genomic Southern hybridization. C. albicans PHO112 null mutants exhibited the following phenotypic properties (P \u3c 0.05) with respect to the wild type counterparts: (1) a reduction of ~25% of phytase activity; (2) a reduction of ~22% of hyphal growth under hyphal-inducing conditions; (3) a reduction of ~22% of adhesion to BECs; and (4) an inability to infect ROHE tissues. Conclusions: The collective data of the present study suggest that C. albicans PHO112 contributes to phytase activity, hyphal development, and fungal virulence. The ability to inhibit the novel virulence trait may provide another antifungal strategy in the fight against this common human fungal pathogen in clinical settings