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 Heterogeneous distribution of Candida albicans cell-surface antigens demonstrated with an Als1-specific monoclonal antibody

Microbiology ◽  
2010 ◽  
Vol 156 (12) ◽  
pp. 3645-3659 ◽  
Author(s):  
David A. Coleman ◽  
Soon-Hwan Oh ◽  
Xiaomin Zhao ◽  
Lois L. Hoyer
Keyword(s):  
Candida Albicans ◽  
Cell Surface ◽  
Spatial Localization ◽  
Host Cells ◽  
Yeast Cells ◽  
Cell Surface Antigens ◽  
Heterogeneous Distribution ◽  
Germ Tubes

Despite an abundance of data describing expression of genes in the Candida albicans ALS (agglutinin-like sequence) gene family, little is known about the production of Als proteins on individual cells, their spatial localization or stability. Als proteins are most commonly discussed with respect to function in adhesion of C. albicans to host and abiotic surfaces. Development of a mAb specific for Als1, one of the eight large glycoproteins encoded by the ALS family, provided the opportunity to detect Als1 during growth of yeast and hyphae, both in vitro and in vivo, and to demonstrate the utility of the mAb in blocking C. albicans adhesion to host cells. Although most C. albicans yeast cells in a saturated culture are Als1-negative by indirect immunofluorescence, Als1 is detected on the surface of nearly all cells shortly after transfer into fresh growth medium. Als1 covers the yeast cell surface, with the exception of bud scars. Daughters of the inoculum cells, and sometimes granddaughters, also have detectable Als1, but Als1 is not detectable on cells from subsequent generations. On germ tubes and hyphae, most Als1 is localized proximal to the mother yeast. Once deposited on yeasts or hyphae, Als1 persists long after the culture has reached saturation. Growth stage-dependent production of Als1, coupled with its persistence on the cell surface, results in a heterogeneous population of cells within a C. albicans culture. Anti-Als1 immunolabelling patterns vary depending on the source of the C. albicans cells, with obvious differences between cells recovered from culture and those from a murine model of disseminated candidiasis. Results from this work highlight the temporal parallels for ALS1 expression and Als1 production in yeasts and germ tubes, the specialized spatial localization and persistence of Als1 on the C. albicans cell surface, and the differences in Als1 localization that occur in vitro and in vivo.

scholarly journals Treatment with Candida albicans biotherapic influences in vitro fungal adhesion to Ma-104 cells

2021 ◽  
Vol 10 (36) ◽  
pp. 152-154
Author(s):  
Beatriz Guerreiro Basílio Costa ◽  
Camila Monteiro Siqueira ◽  
Gleyce Moreno Barbosa ◽  
Venicio Feo Da Veiga ◽  
Maristela Barbosa Portela ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Oral Candidiasis ◽  
Fungal Growth ◽  
Host Cells ◽  
Yeast Cells ◽  
Distilled Water ◽  
Candida Spp ◽  
Morphological Alterations ◽  
Morphological Aspects

Background: Oral candidiasis is an opportunist fungal infection in humans, mainly caused by Candida albicans. It occurs when the host presents an imbalance in the immune system and Candida spp., normally found in human flora, become able to develop the infection [1]. This disease is very common in HIV patients, and in all individuals that present immunossupression, such as patients treated with chemotherapy. Considering this scenario, the development of new medicines to treat oral candidiasis is mandatory. Aims: The aim of this study was to evaluate citotoxicity, morphology and quantify the adhesion rates of C. albicans to biotherapic-treated Ma104 cells. Methodology: The biotherapic was prepared following the Roberto Costa technique and Brazilian Homeopathic Pharmacopeia protocol [2]. Briefly, biotherapic 1X was prepared with 1 mL of aqueous solution containing 108 yeasts of living Candida albicans plus 9 ml of sterile distilled water. This solution was submmited to 100 mechanical succussions. Biotherapic 2X was obtained after addition of 1 ml of 1X solution in 9 ml of sterile distilled water and it was also submitted to 100 mechanical succussions. This procedure was repeated until biotherapic 30X was obtained. As a control, sterile dynamized water (30X) was used. The inhibition of fungal growth induced by biotherapic was evaluated by MTT method after 24 hours of treatment. The morphological aspects of Ma104-biotherapic-treated cells were analyzed by Giemsa staining after 5, 10 and 60 days, and compared with control groups (water 30X and untreated cells). Additionally, Ma104 cells were treated during 5 and 30 days with biotherapic in parallel with respective controls, and the index adhesion of yeast cells was quantified. Results: The biotherapic was not able to reduce the viability of treated C. albicans when compared with controls. On the other hand, Ma104 treated cells presented important morphological alterations after 60 days, such as: cytoplasmic vacuoles, halos around the nucleolus and elongation of the plasmatic membrane. These changes were not observed in ,untreated cells nor in ones treated with water 30X. The adhesion index to Ma104 cells was reduced around 27% after 5 and 30 days of treatment when compared to controls. Conclusion: These results showed that the biotherapic did not present any citotoxicity, but was able to modify the morphological aspects of Ma-104 cells. Additionally, the interaction between host cells and ethilogic agent is directly influenced by biotherapic treatment, suggesting a promising antifungal potential of this medicine.

scholarly journals Reduced Virulence of HWP1-Deficient Mutants of Candida albicans and Their Interactions with Host Cells

2000 ◽  
Vol 68 (4) ◽  
pp. 1997-2002 ◽  
Author(s):  
Noboru Tsuchimori ◽  
Laura L. Sharkey ◽  
William A. Fonzi ◽  
Samuel W. French ◽  
John E. Edwards ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Injury ◽  
Gene Dosage ◽  
Surface Protein ◽  
Host Cells ◽  
Null Mutant ◽  
Gene Dosage Effect ◽  
Hyphal Development

ABSTRACT The Candida albicans gene HWP1 encodes a surface protein that is required for normal hyphal development in vitro. We used mutants lacking one or both alleles of HWP1to investigate the role of this gene in virulence. Mice infected intravenously with the homozygous hwp1 null mutant, CAL3, survived a median of >14 days, whereas mice infected with a control strain containing two functional alleles of HWP1 survived only 3.5 days. After 1 day of infection, all strains produced similar levels of infection in the kidneys, spleen, and blood. However, after 2 and 3 days, there was a significant decrease in the number of organisms in the kidneys of the mice infected with CAL3. This finding suggests that the hwp1 homozygous null mutant is normal in its ability to initiate infection but deficient in its capacity to maintain infection. CAL3 also germinated minimally in the kidneys. The ability of the heterozygous null mutant to germinate and cause mortality in mice was intermediate to CAL3, suggesting a gene dosage effect. To investigate potential mechanisms for the diminished virulence of CAL3, we examined its interactions with endothelial cells and neutrophils in vitro. CAL3 caused less endothelial cell injury than the heterozygoushwp1 mutant. We conclude that the HWP1 gene product is important for both in vivo hyphal development and pathogenicity of C. albicans. Also, the ability to form filaments may be critical for candidal virulence by enabling the fungus to induce cellular injury and maintain a deep-seated infection.

scholarly journals Application of Hydro-ethanol Extract of Tithonia diversifolia (Hemsl) in the Treatment of Experimental Murine Oral Candidiasis

2019 ◽  
pp. 1-10
Author(s):  
Oluwole Moses David ◽  
Margaret Olutayo Alese ◽  
Tobi Oyewole ◽  
Oluwole Ojo Alese ◽  
Adekunle Adegbuyi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Virulence Factors ◽  
Oral Candidiasis ◽  
Ethanolic Extract ◽  
Alcoholic Extract ◽  
Tithonia Diversifolia ◽  
Candida Spp ◽  
Oral Infections

Background: Oral infection caused by Candida spp. is a major healthcare problem in dental and oral care. Treatment failure has been reported in cases of oral candidiasis as a result of resistance to common antifungals. Aim and Objective: In this study, the in vitro and in vivo activities of extract of Tithonia diversifolia against virulence factor-borne and antifungal resistant-Candida albicans were investigated. Candida albicans was isolated from the saliva of patients attending a tertiary hospital in Ekiti State. Methodology: Standard methods were used to determine the presence of virulence factors in the isolates. In vitro and in vivo anti-candidal activities of the hydro-ethanolic extract of T. diversifolia were also tested on the test fungus. Results: The virulence factors have varying percentage of occurrence in all the isolates with catalase having the highest. Itraconazole and nystatin were not effective against the isolates. Out of the six isolates selected (based on antifungal resistance) only three produced strong biofilm. The reduction in the population of the test organisms by the extract was time and concentration dependent. At the end of candidal challenge and treatment assays, extract of T. diversifolia has lower anti-candidal property compared to nystatin. Conclusion: This study has shown that C. albicans associated with the mouth carries virulence factors and are resistant to common antifungals. In this work, we noticed antifungal effects of hydro-alcoholic extract of T. diversifolia on C. albicans associated with oral infections.

scholarly journals Effect of Prolonged Fluconazole Treatment on Candida albicans in Diffusion Chambers Implanted into Mice

2002 ◽  
Vol 46 (10) ◽  
pp. 3175-3179
Author(s):  
Peter G. Sohnle ◽  
Beth L. Hahn
Keyword(s):  
Candida Albicans ◽  
Inflammatory Response ◽  
Inflammatory Cells ◽  
Model System ◽  
Antifungal Drugs ◽  
Yeast Cells ◽  
In Vitro Susceptibility ◽  
Bonferroni Test

ABSTRACT Fluconazole is an azole agent with primarily fungistatic activity in standard in vitro susceptibility tests. The present study was undertaken to develop a diffusion chamber model system in mice in order to study the in vivo effects of prolonged fluconazole treatment on Candida albicans. Chambers containing 100 C. albicans yeast cells were implanted subcutaneously on the flanks of C57BL/6 mice and were then retrieved 6 or 14 weeks later (after fluconazole treatment for 4 or 12 weeks, respectively). Leukocyte counts demonstrated that implantation of the chambers did elicit an inflammatory response but that only small numbers of inflammatory cells were able to enter the chamber interior. Treatment with fluconazole at 10 mg/kg of body weight/day for 12 weeks not only reduced the numbers of viable organisms within the chambers compared to those in untreated mice (mean ± standard deviation of log10 CFU of 0.7 ± 1.2 versus 2.3 ± 2.0; P < 0.001 by the Bonferroni test) but also increased the numbers of chambers that became sterile over the treatment period (14 of 16 versus 6 of 19; P = 0.0009 by the chi-square test). However, treatment for only 4 weeks had minimal effects on the numbers of chamber CFU, and none of the chambers became sterile during this period. Distribution of retrieved organisms between interior fluid and the chamber filters was approximately equal in all the treatment groups. This model system appears to be useful for evaluating the effects of antifungal drugs over prolonged periods in vivo. Its use in the present study demonstrates that fluconazole can increase the rate of sterilization of C. albicans foci that are protected from the host's inflammatory response.

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 Candida albicans enhances the progression of oral squamous cell cancrinoma in vitro and in vivo

2021 ◽  
Author(s):  
Mate Vadovics ◽  
Nora Igaz ◽  
Robert Alfoldi ◽  
David Rakk ◽  
Eva Veres ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Candida Albicans ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Oral Candidiasis ◽  
Marker Genes ◽  
Mesenchymal Transition ◽  
Complex Process

Oral squamous cell carcinoma (OSCC) is a serious health issue worldwide. OSCC is highly associated with oral candidiasis, although it is unclear whether the fungus promotes the genesis and progression of OSCC or cancer facilitates the growth of the fungus. Therefore, we investigated whether Candida could directly influence OSCC development and progression. Our in vitro results suggest that the presence of live C. albicans, but not C. parapsilosis, enhances the progression of OSCC by stimulating the production of matrix metalloproteinases, oncometabolites, pro-tumor signaling routes, and overexpression of prognostic marker genes associated with metastatic events. We also found that oral candidiasis triggered by C. albicans enhanced the progression of OSCC in vivo through the induction of inflammation and overexpression of metastatic genes and markers of epithelial-mesenchymal transition. Taken together, these results suggest that C. albicans actively participates in the complex process of OSCC progression.

scholarly journals Engineered Control of Cell Morphology In Vivo Reveals Distinct Roles for Yeast and Filamentous Forms of Candida albicans during Infection

2003 ◽  
Vol 2 (5) ◽  
pp. 1053-1060 ◽  
Author(s):  
Stephen P. Saville ◽  
Anna L. Lazzell ◽  
Carlos Monteagudo ◽  
Jose L. Lopez-Ribot
Keyword(s):  
Candida Albicans ◽  
Negative Regulator ◽  
Yeast Cells ◽  
Pathogenic Potential ◽  
Infectious Process ◽  
Developmental Transition ◽  
Individual Contributions ◽  
The Individual

ABSTRACT It is widely assumed that the ability of Candida albicans to switch between different morphologies is required for pathogenesis. However, most virulence studies have used mutants that are permanently locked into either the yeast or filamentous forms which are avirulent but unsuitable for discerning the role of morphogenetic conversions at the various stages of the infectious process. We have constructed a strain in which this developmental transition can be externally modulated both in vitro and in vivo. This was achieved by placing one copy of the NRG1 gene (a negative regulator of filamentation) under the control of a tetracycline-regulatable promoter. This modified strain was then tested in an animal model of hematogenously disseminated candidiasis. Mice injected with this strain under conditions permitting hyphal development succumbed to the infection, whereas all of the animals injected under conditions that inhibited this transition survived. Importantly, fungal burdens were almost identical in both sets of animals, indicating that, whereas filament formation appears to be required for the mortality resulting from a deep-seated infection, yeast cells play an important role early in the infectious process by extravasating and disseminating to the target organs. Moreover, these infecting Candida yeast cells still retained their pathogenic potential, as demonstrated by allowing this developmental transition to occur at various time points postinfection. We demonstrate here the importance of morphogenetic conversions in C. albicans pathogenesis. This engineered strain should provide a useful tool in unraveling the individual contributions of the yeast and filamentous forms at various stages of the infectious process.

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