scholarly journals Synergy of Caspofungin with Human Polymorphonuclear Granulocytes for Killing Candida albicans

2010 ◽  
Vol 54 (9) ◽  
pp. 3964-3966 ◽  
Author(s):  
Vivian Tullio ◽  
Narcisa Mandras ◽  
Daniela Scalas ◽  
Valeria Allizond ◽  
Giuliana Banche ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Polymorphonuclear Leukocyte ◽  
Conventional Treatment ◽  
Fungal Infections ◽  
Direct Action ◽  
Therapeutic Option ◽  
Yeast Cells ◽  
Intracellular Killing ◽  
Polymorphonuclear Granulocytes ◽  
Effective Therapeutic Option

ABSTRACT The influence of caspofungin on polymorphonuclear leukocyte (PMN) phagocytosis and intracellular killing of Candida albicans was investigated. Caspofungin, at all of the concentrations tested (2, 3.2, and 8 μg/ml), significantly increased intracellular killing by PMNs through its direct action on both yeast cells and PMNs, indicating the potential ability of caspofungin to synergize with phagocytes for candidal killing. Caspofungin may therefore constitute an effective therapeutic option for the treatment of invasive fungal infections, including those refractory to conventional treatment with azole agents.

scholarly journals Monoclonal antibodies targeting surface exposed epitopes of Candida albicans cell wall proteins confer in vivo protection in an infection model

2021 ◽  
Author(s):  
Soumya Palliyil ◽  
Mark Mawer ◽  
Sami Alwafi ◽  
Lily Fogg ◽  
Giuseppe Buda De Cesare ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fungal Infections ◽  
Yeast Cells ◽  
Infection Model ◽  
Cell Wall Proteins ◽  
Peptide Antigens ◽  
Log Reduction ◽  
Pre Treatment

MAb based immunotherapies targeting systemic and deep-seated fungal infections are still in their early stages of development with currently no licensed antifungal mAbs available. The cell wall glycoproteins of Candida albicans are potential targets for therapeutic antibody generation due to their extracellular location and key involvement in fungal pathogenesis. We describe phage display based generation of recombinant human antibodies specifically targeting two key cell wall proteins (CWPs) in C. albicans - Utr2 and Pga31, using peptide antigens representing the surface exposed regions of CWPs at elevated levels during in vivo infection. Reformatted mAbs preferentially recognised C. albicans hyphal forms compared to yeast cells and an increased binding in cells pre-treated with caspofungin. In macrophage interaction assays, mAb pre-treatment resulted in a faster engulfment of C. albicans cells suggesting opsonophagocytosis. Finally, in a series of clinically predictive, mouse models of systemic candidiasis, our lead mAb achieved an improved survival (83%) and several log reduction of fungal burden in the kidneys, similar to levels achieved for the fungicidal drug caspofungin, and superior to any anti-Candida mAb.

scholarly journals Effects ofMentha suaveolensEssential Oil Alone or in Combination with Other Drugs inCandida albicans

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Annarita Stringaro ◽  
Elisabetta Vavala ◽  
Marisa Colone ◽  
Federico Pepi ◽  
Giuseppina Mignogna ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Candida Albicans ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Yeast Cells ◽  
Cellular Damage ◽  
Prolonged Treatment ◽  
Microbial Biofilms ◽  
Transmission Electron ◽  
Morphological Differences

Candidosis is the most important cause of fungal infections in humans. The yeastCandida albicanscan form biofilms, and it is known that microbial biofilms play an important role in human diseases and are very difficult to treat. The prolonged treatment with drugs has often resulted in failure and resistance. Due to the emergence of multidrug resistance, alternatives to conventional antimicrobial therapy are needed. This study aims to analyse the effects induced by essential oil ofMentha suaveolensEhrh (EOMS) onCandida albicansand its potential synergism when used in combination with conventional drugs. Morphological differences between control and EOMS treated yeast cells or biofilms were observed by scanning electron microscopy and transmission electron microscopy (SEM and TEM resp.,). In order to reveal the presence of cell cycle alterations, flow cytometry analysis was carried out as well. The synergic action of EOMS was studied with the checkerboard method, and the cellular damage induced by different treatments was analysed by TEM. The results obtained have demonstrated both the effects of EOMS onC. albicansyeast cells and biofilms and the synergism of EOMS when used in combination with conventional antifungal drugs as fluconazole (FLC) and micafungin (MCFG), and therefore we can hypothesize on its potential use in therapy. Further studies are necessary to know its mechanism of action.

scholarly journals Saccharomyces cerevisiae and Candida albicans Yeast Cells Labeled with Fe(III) Complexes as MRI Probes

2020 ◽  
Vol 6 (3) ◽  
pp. 41
Author(s):  
Akanksha Patel ◽  
Didar Asik ◽  
Eric M. Snyder ◽  
Joseph A. Spernyak ◽  
Paul J. Cullen ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Candida Albicans ◽  
Fungal Infections ◽  
Bound Water ◽  
Yeast Cells ◽  
Water Proton ◽  
Proton Relaxation ◽  
Spectra Analysis ◽  
Antibiotic Resistant ◽  
Fluorescence Dye

The development of MRI probes is of interest for labeling antibiotic-resistant fungal infections based on yeast. Our work showed that yeast cells can be labeled with high-spin Fe(III) complexes to produce enhanced T2 water proton relaxation. These Fe(III)-based macrocyclic complexes contained a 1,4,7-triazacyclononane framework, two pendant alcohol groups, and either a non-coordinating ancillary group and a bound water molecule or a third coordinating pendant. The Fe(III) complexes that had an open coordination site associated strongly with Saccharomyces cerevisiae upon incubation, as shown by screening using Z-spectra analysis. The incubation of one Fe(III) complex with either Saccharomyces cerevisiae or Candida albicans yeast led to an interaction with the β-glucan-based cell wall, as shown by the ready retrieval of the complex by the bidentate chelator called maltol. Other conditions, such as a heat shock treatment of the complexes, produced Fe(III) complex uptake that could not be reversed by the addition of maltol. Appending a fluorescence dye to Fe(TOB) led to uptake through secretory pathways, as shown by confocal fluorescence microscopy and by the incomplete retrieval of the Fe(III) complex by the maltol treatment. Yeast cells that were labeled with these Fe(III) complexes displayed enhanced water proton T2 relaxation, both for S. cerevisiae and for yeast and hyphal forms of C. albicans.

scholarly journals Impaired immune response to Candida albicans in aged mice

2006 ◽  
Vol 55 (12) ◽  
pp. 1649-1656 ◽  
Author(s):  
Celia Murciano ◽  
Eva Villamón ◽  
Alberto Yáñez ◽  
José-Enrique O'Connor ◽  
Daniel Gozalbo ◽  
...  
Keyword(s):  
Immune Response ◽  
Candida Albicans ◽  
Fungal Infections ◽  
Acquired Resistance ◽  
Yeast Cells ◽  
T Helper 1 ◽  
Aged Mice ◽  
Old Mice ◽  
Young Mice

The prevalence of opportunistic fungal infections has increased dramatically among the aged population in recent years. This work investigated the effect of ageing on murine defences against Candida albicans. Aged C57BL/6 mice that were experimentally infected intravenously had a significantly impaired survival and a higher tissue fungal burden compared with young mice. In vitro production of tumour necrosis factor (TNF)-α by macrophages from aged mice in response to yeast cells and hyphae of C. albicans was significantly lower than production by macrophages from young mice. In vitro production of cytokines, such as TNF-α and gamma interferon (IFN-γ), by antigen-stimulated splenocytes from mice intravenously infected with C. albicans cells was also diminished in old mice. This decrease in production of T helper 1 cytokines in old mice correlated with a diminished frequency of IFN-γ-producing CD4+ T lymphocytes, although the ability to develop an acquired resistance upon vaccination (primary sublethal infection) of mice with the low-virulence PCA2 strain was not affected in aged mice. The diversity of antigens recognized by C. albicans-specific antibodies in sera from infected aged mice was clearly diminished when compared with that from infected young mice. Taken together, these data show that aged mice develop an altered innate and adaptive immune response to C. albicans and are more susceptible to systemic primary candidiasis.

Candida albicans and its metabolite gliotoxin inhibit platelet function via interaction with thiols

2010 ◽  
Vol 104 (08) ◽  
pp. 270-278 ◽  
Author(s):  
Anne Bertling ◽  
Silke Niemann ◽  
Andreas Uekötter ◽  
Wolfgang Fegeler ◽  
Cornelia Lass-Flörl ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Platelet Function ◽  
Fungal Infections ◽  
Reduced Glutathione ◽  
Disulfide Bridge ◽  
Blood Stream ◽  
Inhibitory Effect ◽  
Yeast Cells ◽  
Dependent Manner ◽  
Fibrinogen Binding

SummaryPlatelets bind to Candida albicans, the major cause of candidiasis. But in contrast to other microorganisms the fungus does not aggregate platelets. Gliotoxin (GT), which possesses immunosuppressive properties, is produced by various fungi, including the opportunistic pathogens Aspergillus fumigatus and C. albicans. Its mode of action involves the formation of mixed disulfides with host proteins. Disulfide exchanges play an important role in platelet activation. Therefore, the effect of C. albicans and GT on platelet function was tested. C. albicans yeast cells (5,000–10,000 cells/μl) and GT, in pathophysiologically relevant concentrations (0.05–0.5 μM), inhibited platelet fibrinogen binding, anti gp IIb/IIIa antibody PAC-1 binding, aggregation and procoagulant activity in a dose-dependent manner. Alpha granule release, measured via CD62P surface expression, was not affected. Addition of reduced glutathione partially counteracted the effect of C. albicans and GT on platelet fibrinogen binding and platelet aggregation. The C. albicans metabolite GT features antithrombotic properties in addition to its immunosuppressive functions. Since treatment with reduced glutathione partially counteracted the inhibitory effect of C. albicans yeast cells and GT on platelet fibrinogen binding, the antithrombotic activity is likely to depend on the disulfide bridge of this mycotoxin. GT production by C. albicans could contribute to its survival in the blood stream during vascular infections. The knowledge of the underlying mechanisms of the antithrombotic properties might help to treat fungal infections as well as thrombosis.

Adherence and Biofilm Formation in Candida albicans Strains Isolated from Different Infection Sites in Hospitalized Patients

2018 ◽  
Vol 68 (12) ◽  
pp. 2832-2835
Author(s):  
Omar Sadik ◽  
Lia Mara Ditu ◽  
Irina Gheorghe ◽  
Gratiela Gradisteanu Pircalabioru ◽  
Coralia Bleotu ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Respiratory Tract ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Morphological Characteristics ◽  
Stool Culture ◽  
Yeast Cells ◽  
Upper Respiratory Tract ◽  
Adherence Pattern

Adherence of Candida albicans to the cellular and inert substratum contributes to its commensal status, but also plays an essential role in the development of fungal infections, particularly in hospitalized and immunodepressed patients. This study evaluated the adherence capacity and biofilm formation of 109 C. albicans strains isolated from upper respiratory tract secretions, wound secretions, urine culture, blood culture and stool culture taken from patients hospitalized for cardiovascular surgery. The strains were originally identified as C. albicans, based on their morphological characteristics and then confirmed by the Vitek II automatic system. All tested strains adhered to the cellular substratum, the isolates from stool culture, urine and thrush secretion exhibiting the most intensive adhesion capacity, the predominant adherence pattern being the aggregative one. Patient age and gender did not exhibit a significant influence on the adhesion process. The strains with the highest biofilm production capacity were the ones isolated from respiratory tract secretions and urine cultures. Statistically significant correlations could be established among a high number of yeast cells adhered to HeLa cells and i) the aggregative adherence pattern and ii) the moderate to high capacity to form biofilms on the inert substratum. These results could suggest the implication of common fungal structures in the colonization of inert and cellular substrata, while the elucidation of the molecular mechanisms involved in these processes could bring an important benefit to the appropriate management of fungal infections, depending on the isolation source.

Ultrastructural Changes of Candida albicans Species Induced by the Presence of Sodium Diclofenac

2017 ◽  
Vol 68 (11) ◽  
pp. 2566-2569 ◽  
Author(s):  
Elena Rusu ◽  
Ionela Sarbu ◽  
Magdalena Mitache ◽  
Horatiu Moldovan ◽  
Carmen Ioana Biris ◽  
...  
Keyword(s):  
Candida Albicans ◽  
High Frequency ◽  
Fungal Infections ◽  
Diagnostic Methods ◽  
Ultrastructural Changes ◽  
Frequency Of Occurrence ◽  
Medical Treatments ◽  
Sodium Diclofenac ◽  
Cell Wall Disruption ◽  
Candidiasis Treatment

The high frequency of occurrence of candidiasis as well as high mortality of patients with immunosuppression cause a tendency toward better understanding of Candida albicans species virulence factors and developing sensitive and specific diagnostic methods, and appropriate strategies of candidiasis treatment. In recent decades the incidence of fungal infections has alarming increases because of advanced medical treatments. In this study was analyzed possible ultrastructural changes of the species C. albicans cells following treatment with sodium diclofenac at various concentrations. Following treatment of C. albicans cells with sodium diclofenac 1 mM and 2 mM changes in the plasmalemma can be noticed, changes in the density of cell wall, disruption and necrotic appearance of the cytoplasm.

Efficacy of Novel Schiff base Derivatives as Antifungal Compounds in Combination with Approved Drugs Against Candida Albicans

2019 ◽  
Vol 15 (6) ◽  
pp. 648-658 ◽  
Author(s):  
Manzoor Ahmad Malik ◽  
Shabir Ahmad Lone ◽  
Parveez Gull ◽  
Ovas Ahmad Dar ◽  
Mohmmad Younus Wani ◽  
...  
Keyword(s):  
Schiff Base ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Fungal Infections ◽  
Total Sterol ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Ergosterol Biosynthesis ◽  
Dependent Manner ◽  
Schiff Base Derivatives

Background: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required. Methods: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates. Results: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies. Conclusion: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds.

scholarly journals Convalescent Plasma Therapy: An Effective Therapeutic Option to Treat COVID-19? A Narrative Review

2020 ◽  
Vol Volume 8 ◽  
pp. 7-21
Author(s):  
Ishita Ray ◽  
Diana Fiorela Sánchez ◽  
Chris Andrea Robert ◽  
Mary Phyllis Robert
Keyword(s):  
Therapeutic Option ◽  
Narrative Review ◽  
Plasma Therapy ◽  
Effective Therapeutic Option
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