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Candida

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Candida
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In conjunction with the Candida and Candidiasis meeting, Microbiology Society is bringing together research on Candida biology – species that are major causes of infectious disease in AIDS patients, cancer chemotherapy patients, premature infants, etc. The polymorphic yeast Candida albicans is the most important fungal pathogen in humans. Beyond the clinics, basic research in this organism deals with a variety of topics of interest, like the genetics and molecular biology behind antifungal drug resistance; the molecular determinants of endurance to nutritional, pH and oxidative stress imposed by the host defences; or its interactions with both the host epithelia and bacterial partners that share the mucosal microbiota with the fungus. This collection of research articles published on diverse aspects of Candida biology showcases the journals’ range of Candida research. This collection is open for submissions across our portfolio. Authors are invited to submit on any aspect of Candida research. Upon submission, please indicate that your manuscript is to be considered for the Candida collection.

Collection Contents

4 results

    • Antifungal activity of human antimicrobial peptides targeting apoptosis in

      Innovative antifungal therapies are of crucial importance to combat the potentially life-threatening infections linked to the multidrug-resistant fungal pathogen . Induction of regulated cell death, apoptosis, could provide an outline for future therapeutics. Human antimicrobial peptides (AMPs), well-known antifungal compounds, have shown the ability to induce apoptosis in pathogenic fungi.

      Although it is known that AMPs possess antifungal activity against , their ability to induce apoptosis requires further investigations.

      This study evaluated the effects of AMPs on the induction of apoptosis in .

      Human neutrophil peptide-1 (HNP-1), human β-Defensins-3 (hBD-3) and human salivary histatin 5 (His 5) were assessed against two clinical isolates. Apoptosis hallmarks were examined using FITC-Annexin V/PI double labelling assay and terminal deoxynucleotidyl transferase deoxynucleotidyl transferase nick-end labelling (TUNEL) to detect phosphatidylserine externalization and DNA fragmentation, respectively. Then, several intracellular triggers were studied using JC-10 staining, spectrophotometric assay and 2′,7′-dichlorofluorescin diacetate staining to measure the mitochondrial membrane potential, cytochrome-c release and reactive oxygen species (ROS) production, respectively.

      FITC-Annexin V/PI staining and TUNEL analysis revealed that exposure of cells to HNP-1 and hBD-3 triggered both early and late apoptosis, while His 5 caused significant necrosis. Furthermore, HNP-1 and hBD-3 induced significant mitochondrial membrane depolarization, which resulted in substantial cytochrome c release. In contrast to His 5, which showed minimal mitochondrial depolarization and no cytochrome c release. At last, all peptides significantly increased ROS production, which is related to both types of cell death. Therefore, these peptides represent promising and effective antifungal agents for treating invasive infections caused by multidrug-resistant

    • Antifungal susceptibilities, biofilms, phospholipase and proteinase activities in the Candida rugosa complex and Candida pararugosa isolated from tertiary teaching hospitals

      Purpose. Non-albicans Candida species have emerged as fungal pathogens that cause invasive infections, with many of these species displaying resistance to commonly used antifungal agents. This study was confined to studying the characteristics of clinical isolates of the C. rugosa complex and C. pararugosa species.

      Methodology. Seven isolates of the C. rugosa complex and one isolate of C. pararugosa were obtained from two tertiary referral hospitals in Malaysia. Their antifungal susceptibilities, biofilm, proteinase, phospholipase, esterase and haemolysin activities were characterized. Biofilms were quantified using crystal violet (CV) and tetrazolium (XTT) reduction assays at 1.5, 6, 18, 24, 48 and 72 h.

      Results/Key findings. The E-test antifungal tests showed that both species have elevated MICs compared to C. albicans and C. tropicalis. The highest biomass was observed in one of the C. rugosa isolates (0.237), followed by C. pararugosa (0.206) at 18 h of incubation. However, the highest bioactivity was observed in the C. rugosa ATCC 10571 strain at 24 h (0.075), followed by C. pararugosa at 48 h (0.048) and the same C. rugosa strain at 24 h (0.046), with P<0.05. All isolates exhibited high proteinase activity (+++) whereas six isolates showed very strong esterase activity (++++). All the isolates were alpha haemolytic producers. None of the isolates exhibited phospholipase activity.

      Conclusion. Elevated MICs were shown for the C. rugosa complex and C. pararugosa for commonly used antifungal drugs. Further studies to identify virulence genes involved in the pathogenesis and genes that confer reduced drug susceptibility in these species are proposed.

    • Antifungal susceptibility and virulence of species complex: an overview of their pathogenic potential

      Antifungal resistance and several putative virulence factors have been associated with the pathogenicity of the species complex. The objective of this study was to evaluate the antifungal susceptibility, the production of virulence factors and the pathogenicity of the complex.

      Overall, 49 isolates of , 19 and nine were used. The planktonic and biofilm susceptibility to fluconazole, itraconazole, voriconazole, amphotericin B and caspofungin was assessed using a broth microdilution assay. Finally, the production of biofilm and hydrolytic enzymes and the fungal pathogenicity against were investigated.

      Overall, one was resistant to caspofungin and susceptible-dose-dependent to itraconazole, the other two were susceptible-dose-dependent to fluconazole and itraconazole, and one was susceptible-dose-dependent to azoles. A total of 67.5 % of the isolates were biofilm producers. Amphotericin B and caspofungin caused the greatest reduction in the metabolic activity and biomass of mature biofilms. Phospholipase and protease production was observed in 55.1 % of , 42.1 % of and 33.3 % of isolates. Moreover, 57.9 % of and 20.4 % of isolates were β-haemolytic, and all were α-haemolytic. Finally, the complex caused high mortality of after 96 h of exposure.

      These results reinforce the heterogeneity of these cryptic species for their antifungal susceptibility, virulence and pathogenic potential, emphasizing the relevance of monitoring these emerging pathogens.

    • Anti-inflammatory effect of two strains during infection with and in a HeLa cell culture model

      Lactobacilli are the dominant bacteria of the vaginal tract of healthy women and they play a major role in the maintenance of mucosal homeostasis, preventing genital infections, such as bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). It is now known that one mechanism of this protection is the influence that lactobacilli can exert on host immune responses. In this context, we evaluated two strains ( 59 and 137) for their immunomodulatory properties in response to (BV) or (VVC) infections in a HeLa cell infection model. and triggered the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) and the activation of NF-κB in HeLa cells, in contrast to 59 and 137. Treatments with the strains or their cell-free supernatants before (pre-treatment) or after (post-treatment) the challenge with the pathogens resulted in decreased secretion of pro-inflammatory cytokines and decreased activation of NF-κB. The treatments with strains not only decreased the secretion of IL-8, but also its expression, as confirmed by gene reporter luciferase assay, suggesting transcription-level control by lactobacilli. In conclusion, 59 and 137 were confirmed to have an anti-inflammatory effect against and and they were able to influence signalling in NF-κB pathway, making them interesting candidates as probiotics for the prevention or treatment of BV and VVC.

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