scholarly journals Candida albicans Biofilm-Defective Mutants

2005 ◽  
Vol 4 (8) ◽  
pp. 1493-1502 ◽  
Author(s):  
Mathias L. Richard ◽  
Clarissa J. Nobile ◽  
Vincent M. Bruno ◽  
Aaron P. Mitchell
Keyword(s):  
Candida Albicans ◽  
Early Phase ◽  
Intermediate Phase ◽  
Significant Risk ◽  
Life Cycles ◽  
Media Analysis ◽  
Yeast Cells ◽  
Phase Arrest ◽  
Biofilm Development

ABSTRACT Biofilm formation plays a key role in the life cycles and subsistence of many microorganisms. For the human fungal pathogen Candida albicans, biofilm development is arguably a virulence trait, because medical implants that serve as biofilm substrates are significant risk factors for infection. The development of C. albicans biofilms in vitro proceeds through an early phase, in which yeast cells populate a substrate, an intermediate phase, in which pseudohyphal and hyphal cell types are produced, and a maturation phase, in which continued cell growth is accompanied by accumulation of an extracellular matrix. Here we report the results of a screen for C. albicans biofilm-defective mutants, in which homozygous insertions in NUP85, MDS3, KEM1, and SUV3 were found to block biofilm development. Confocal microscopic examination suggests that nup85, suv3, and mds3 mutations cause early-phase arrest, whereas the kem1 mutation causes intermediate-phase arrest. All of the mutants are defective in hypha production in several media. Analysis of mixed-biofilm development indicates that all of the mutants are defective in the production of hyphae in the context of a biofilm. Because all of the mutants are defective in the retention of cells in the biofilm, we infer that hyphae provide an adherent scaffold that stabilizes the biofilm structure.

scholarly journals Anti-Candidal Activity and In Vitro Cytotoxicity Assessment of Graphene Nanoplatelets Decorated with Zinc Oxide Nanorods

Nanomaterials ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 752 ◽  
Author(s):  
Graziella Ficociello ◽  
Maria De Caris ◽  
Giusy Trillò ◽  
Domenico Cavallini ◽  
Maria Sarto ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Candida Albicans ◽  
Pathogenic Fungus ◽  
In Vitro Cytotoxicity ◽  
Yeast Cells ◽  
Zinc Oxide Nanorods ◽  
Aggregation State ◽  
Oxide Nanorods ◽  
Biofilm Development

Candida albicans is the most common pathogenic fungus that is isolated in nosocomial infections in medically and immune-compromised patients. The ability of C. albicans to convert its form from yeast to hyphal morphology contributes to biofilm development that effectively shelters Candida against the action of antifungals molecules. In the last years, nanocomposites are the most promising solutions against drug-resistant microorganisms. The aim of this study was to investigate the antifungal activity of graphene nanoplateles decorated with zinc oxide nanorods (ZNGs) against the human pathogen Candida albicans. We observed that ZNGs were able to induce a significant mortality in fungal cells, as well as to affect the main virulence factors of this fungus or rather the hyphal development and biofilm formation. Reactive Oxygen Species (ROS) formation in yeast cells resulted one of the mechanisms of ZNGs to induce mortality. Finally, the toxicity of this nanomaterial was tested also on human keratinocyte cell line HaCaT. Our data indicated that ZNGs resulted not toxic when their aggregation state decreased by adding glycerol as emulsifier to ZNGs suspensions or when HaCaT cells were grown on ZNGs-coated glasses. Overall, the results that were obtained indicated that ZNGs could be exploited as an antifungal nanomaterial with a high degree of biocompatibility on human cells.

scholarly journals Sustained Nitric Oxide-Releasing Nanoparticles Induce Cell Death in Candida albicans Yeast and Hyphal Cells, Preventing Biofilm FormationIn Vitroand in a Rodent Central Venous Catheter Model

2016 ◽  
Vol 60 (4) ◽  
pp. 2185-2194 ◽  
Author(s):  
Mohammed S. Ahmadi ◽  
Hiu Ham Lee ◽  
David A. Sanchez ◽  
Adam J. Friedman ◽  
Moses T. Tar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Candida Albicans ◽  
Flow Cytometric Analysis ◽  
Extracellular Polysaccharide ◽  
Host Cells ◽  
Yeast Cells ◽  
Central Venous ◽  
Content Type ◽  
Biofilm Development

ABSTRACTCandida albicansis a leading nosocomial pathogen. Today, candidal biofilms are a significant cause of catheter infections, and such infections are becoming increasingly responsible for the failure of medical-implanted devices.C. albicansforms biofilms in which fungal cells are encased in an autoproduced extracellular polysaccharide matrix. Consequently, the enclosed fungi are protected from antimicrobial agents and host cells, providing a unique niche conducive to robust microbial growth and a harbor for recurring infections. Here we demonstrate that a recently developed platform comprised of nanoparticles that release therapeutic levels of nitric oxide (NO-np) inhibits candidal biofilm formation, destroys the extracellular polysaccharide matrices of mature fungal biofilms, and hinders biofilm development on surface biomaterials such as the lumen of catheters. We found NO-np to decrease both the metabolic activity of biofilms and the cell viability ofC. albicansin vitroandin vivo. Furthermore, flow cytometric analysis found NO-np to induce apoptosis in biofilm yeast cellsin vitro. Moreover, NO-np behave synergistically when used in combination with established antifungal drug therapies. Here we propose NO-np as a novel treatment modality, especially in combination with standard antifungals, for the prevention and/or remediation of fungal biofilms on central venous catheters and other medical devices.

scholarly journals Synergism of Streptococcus mutans and Candida albicans Reinforces Biofilm Maturation and Acidogenicity in Saliva: An In Vitro Study

2021 ◽  
Vol 10 ◽  
Author(s):  
Hye-Eun Kim ◽  
Yuan Liu ◽  
Atul Dhall ◽  
Marwa Bawazir ◽  
Hyun Koo ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Critical Role ◽  
In Vitro Study ◽  
Acidic Ph ◽  
Acidic Environment ◽  
Symbiotic Interaction ◽  
Biofilm Development

Early childhood caries, a virulent-form of dental caries, is painful, difficult, and costly to treat that has been associated with high levels of Streptococcus mutans (Sm) and Candida albicans (Ca) in plaque-biofilms on teeth. These microorganisms appear to develop a symbiotic cross-kingdom interaction that amplifies the virulence of plaque-biofilms. Although biofilm studies reveal synergistic bacterial-fungal association, how these organisms modulate cross-kingdom biofilm formation and enhance its virulence in the presence of saliva remain largely unknown. Here, we compared the properties of Sm and Sm-Ca biofilms cultured in saliva by examining the biofilm structural organization and capability to sustain an acidic pH environment conducive to enamel demineralization. Intriguingly, Sm-Ca biofilm is rapidly matured and maintained acidic pH-values (~4.3), while Sm biofilm development was retarded and failed to create an acidic environment when cultured in saliva. In turn, the human enamel slab surface was severely demineralized by Sm-Ca biofilms, while there was minimal damage to the enamel surface by Sm biofilm. Interestingly, Sm-Ca biofilms exhibited an acidic environment regardless of their hyphal formation ability. Our data reveal the critical role of symbiotic interaction between S. mutans and C. albicans in human saliva in the context of pathogenesis of dental caries, which may explain how the cross-kingdom interaction contributes to enhanced virulence of plaque-biofilm in the oral cavity.

scholarly journals In Vitro Activity of Caspofungin against Candida albicans Biofilms

2002 ◽  
Vol 46 (11) ◽  
pp. 3591-3596 ◽  
Author(s):  
Stefano P. Bachmann ◽  
Kacy VandeWalle ◽  
Gordon Ramage ◽  
Thomas F. Patterson ◽  
Brian L. Wickes ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inhibitory Effect ◽  
Vitro Activity ◽  
Confocal Scanning Laser Microscopy ◽  
In Vitro Activity ◽  
Confocal Scanning ◽  
Confocal Scanning Laser ◽  
Biofilm Development ◽  
Candida Albicans Biofilms

ABSTRACT Most manifestations of candidiasis are associated with biofilm formation on biological or inanimate surfaces. Candida albicans biofilms are recalcitrant to treatment with conventional antifungal therapies. Here we report on the activity of caspofungin, a new semisynthetic echinocandin, against C. albicans biofilms. Caspofungin displayed potent in vitro activity against sessile C. albicans cells within biofilms, with MICs at which 50% of the sessile cells were inhibited well within the drug's therapeutic range. Scanning electron microscopy and confocal scanning laser microscopy were used to visualize the effects of caspofungin on preformed C. albicans biofilms, and the results indicated that caspofungin affected the cellular morphology and the metabolic status of cells within the biofilms. The coating of biomaterials with caspofungin had an inhibitory effect on subsequent biofilm development by C. albicans. Together these findings indicate that caspofungin displays potent activity against C. albicans biofilms in vitro and merits further investigation for the treatment of biofilm-associated infections.

The ultrastructure of Candida albicans infections

1981 ◽  
Vol 27 (11) ◽  
pp. 1156-1164 ◽  
Author(s):  
Thomas J. Marrie ◽  
J. William Costerton
Keyword(s):  
Candida Albicans ◽  
Oral Candidiasis ◽  
Ruthenium Red ◽  
Host Cells ◽  
Yeast Cells ◽  
Positive Matrix ◽  
Urine Sediment ◽  
Bacteria Adhesion

Scrapings of Candida albicans plaques from the tongue and buccal mucosa of patients with oral candidiasis were examined electron microscopy. In addition, urine sediment from patients with infection of their catheterized urinary tracts was similar examined. Three types of C. albicans – oral epithelial cell interactions were noted: a loose adherence apparently mediated by ruthenium red positive matrix, a "tight" adherence where no space could be seen between the host and yeast cell, and invasions host cells by yeast hyphal elements. Adhesion of Candida blastospores to hyphal elements and adhesion of bacteria to Candida cells was also frequently observed.Urine sediments from patients with mixed bacteria–yeast infections demonstrated adhesion of the bacteria to the yeast cells. This phenomenon was also demonstrated in in vitro experiments and fibrous ruthenium red material invariably occupied the zo*** of adhesion.Phagocytosis of yeast by polymorphonuclear leukocytes was found in urinary, but not in oral, candidiasis. Our in vivo and vitro observations indicate that a ruthenium red positive matrix covers the surfaces involved in the yeast to yeast, yeast to ho and yeast to bacteria adhesion.

scholarly journals The “Finger,” a Unique Multicellular Morphology of Candida albicans Induced by CO2and Dependent upon the Ras1-Cyclic AMP Pathway

2012 ◽  
Vol 11 (10) ◽  
pp. 1257-1267 ◽  
Author(s):  
Karla J. Daniels ◽  
Claude Pujol ◽  
Thyagarajan Srikantha ◽  
David R. Soll
Keyword(s):  
Candida Albicans ◽  
Cyclic Amp ◽  
Mutational Analysis ◽  
Cell Monolayer ◽  
Yeast Cells ◽  
Content Type ◽  
Dispersal Mechanism ◽  
Basal Bulb ◽  
High Doses

ABSTRACTMost experiments exploring the basic biology of pathogenic microbes are performedin vitrounder conditions that do not usually mimic those of their host niche. Hence, developmental programs initiated by specific host cues may be missedin vitro. We have tested the effects of growing low-density agar cultures of the yeast pathogenCandida albicansin concentrations of CO2found in the gastrointestinal tract. It is demonstrated that in physiological concentrations of CO2at 37°C, yeast cells form a heretofore undescribed multicellular “finger” morphology distinct from a previously described stalk-like structure induced by high doses of UV irradiation that kills more than 99.99% of cells. The finger extends aerially, is uniform in diameter, and is visible to the naked eye, attaining lengths of 3 mm. It is composed of a basal yeast cell monolayer adhering to a semispherical crater formed in the agar and connected to a basal bulb of yeast cells at a fragile interface. The bulb extends into the long shaft. We propose that a single, centrally located hypha extending the length of the shaft forms buds at compartment junctions that serve as the source of the yeast cells in the shaft. A mutational analysis reveals finger formation is dependent upon the pathway Ras1→Cdc35→cyclic AMP (cAMP) (PDE2—|)→Tpk2→Tec1. Because of the mechanically fragile interface and the compactness of bulb and shaft, we suggest that the finger may function as a multicellular dispersal mechanism produced in host niches containing high levels of CO2.

scholarly journals Effect of fluconazole on viability of Candida albicans over extended periods of time.

1996 ◽  
Vol 40 (11) ◽  
pp. 2622-2625 ◽  
Author(s):  
P G Sohnle ◽  
B L Hahn ◽  
M D Erdmann
Keyword(s):  
Candida Albicans ◽  
Marked Reduction ◽  
Culture Medium ◽  
Antimicrobial Agents ◽  
Yeast Cells ◽  
In Vitro Susceptibility ◽  
Fungistatic Activity ◽  
Susceptibility Tests ◽  
Infecting Organisms

The treatment of chronic mycoses may expose the infecting organisms to antimicrobial agents for extended periods of time. It is possible that an azole antifungal drug such as fluconazole, with primarily fungistatic activity in standard in vitro susceptibility tests, might be able to damage the fungal cells and reduce their viability over prolonged incubations under nonproliferating conditions. To test this possibility, Candida albicans yeast cells were exposed to various concentrations of fluconazole in RPMI 1640 tissue culture medium for 4 h at 37 degrees C, washed free of the drug, and then incubated at 37 degrees C for a 28-day period; enumeration of the remaining CFU at various times during this period revealed no increased loss of viability for the fluconazole-exposed organisms. However, when fluconazole was added to the organisms maintained in distilled water (with or without pretreatment with the drug), a marked reduction of viability was found. At 14 days of incubation with two strains of C. albicans, negative cultures were found for 7 of 10 and 10 of 11 samples, respectively, containing 1.0 microgram of fluconazole per ml versus 0 of 10 and 1 of 11 control samples (P of < 0.01 and 0.001, respectively). The effect of fluconazole on fungal viability under these conditions became noticeable at approximately 7 days and was greater when the samples were incubated at 37 degrees C rather than 25 degrees C. These findings suggest that fluconazole may have fungicidal effects on fungal cells during prolonged exposures under conditions in which the organisms are prevented from proliferating by lack of nutrients.

scholarly journals Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque BiofilmsIn Vivo

2014 ◽  
Vol 82 (5) ◽  
pp. 1968-1981 ◽  
Author(s):  
Megan L. Falsetta ◽  
Marlise I. Klein ◽  
Punsiri M. Colonne ◽  
Kathleen Scott-Anne ◽  
Stacy Gregoire ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Bacterial Pathogen ◽  
Single Species ◽  
Content Type ◽  
3 Dimensional ◽  
Biofilm Development

ABSTRACTStreptococcus mutansis often cited as the main bacterial pathogen in dental caries, particularly in early-childhood caries (ECC).S. mutansmay not act alone;Candida albicanscells are frequently detected along with heavy infection byS. mutansin plaque biofilms from ECC-affected children. It remains to be elucidated whether this association is involved in the enhancement of biofilm virulence. We showed that the ability of these organisms together to form biofilms is enhancedin vitroandin vivo. The presence ofC. albicansaugments the production of exopolysaccharides (EPS), such that cospecies biofilms accrue more biomass and harbor more viableS. mutanscells than single-species biofilms. The resulting 3-dimensional biofilm architecture displays sizeableS. mutansmicrocolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich matrix. Using a rodent model, we explored the implications of this cross-kingdom interaction for the pathogenesis of dental caries. Coinfected animals displayed higher levels of infection and microbial carriage within plaque biofilms than animals infected with either species alone. Furthermore, coinfection synergistically enhanced biofilm virulence, leading to aggressive onset of the disease with rampant carious lesions. Ourin vitrodata also revealed that glucosyltransferase-derived EPS is a key mediator of cospecies biofilm development and that coexistence withC. albicansinduces the expression of virulence genes inS. mutans(e.g.,gtfB,fabM). We also found thatCandida-derived β1,3-glucans contribute to the EPS matrix structure, while fungal mannan and β-glucan provide sites for GtfB binding and activity. Altogether, we demonstrate a novel mutualistic bacterium-fungus relationship that occurs at a clinically relevant site to amplify the severity of a ubiquitous infectious disease.

scholarly journals Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

2016 ◽  
Vol 60 (8) ◽  
pp. 4519-4529 ◽  
Author(s):  
Harry C. Pappas ◽  
Rina Sylejmani ◽  
Matthew S. Graus ◽  
Patrick L. Donabedian ◽  
David G. Whitten ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Membrane Integrity ◽  
Significant Risk ◽  
Yeast Cells ◽  
Size Difference ◽  
Phenylene Ethynylene ◽  
Biocidal Activity ◽  
Content Type ◽  
Antifungal Properties ◽  
Phenylene Ethynylenes

ABSTRACTCandidaspecies are the cause of many bloodstream infections through contamination of indwelling medical devices. These infections account for a 40% mortality rate, posing a significant risk to immunocompromised patients. Traditional treatments againstCandidainfections include amphotericin B and various azole treatments. Unfortunately, these treatments are associated with high toxicity, and resistant strains have become more prevalent. As a new frontier, light-activated phenylene ethynylenes have shown promising biocidal activity against Gram-positive and -negative bacterial pathogens, as well as the environmental yeastSaccharomyces cerevisiae. In this study, we monitored the viability ofCandidaspecies after treatment with a cationic conjugated polymer [poly(p-phenylene ethynylene); PPE] or oligomer [“end-only” oligo(p-phenylene ethynylene); EO-OPE] by flow cytometry in order to explore the antifungal properties of these compounds. The oligomer was found to disruptCandida albicansyeast membrane integrity independent of light activation, while PPE is able to do so only in the presence of light, allowing for some control as to the manner in which cytotoxic effects are induced. The contrast in killing efficacy between the two compounds is likely related to their size difference and their intrinsic abilities to penetrate the fungal cell wall. Unlike EO-OPE-DABCO (where DABCO is quaternized diazabicyclo[2,2,2]octane), PPE-DABCO displayed a strong propensity to associate with soluble β-glucan, which is expected to inhibit its ability to access and perturb the inner cell membrane ofCandidayeast. Furthermore, treatment with PPE-DABCO unmaskedCandida albicansβ-glucan and increased phagocytosis by Dectin-1-expressing HEK-293 cells. In summary, cationic phenylene ethynylenes show promising biocidal activity against pathogenicCandidayeast cells while also exhibiting immunostimulatory effects.

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