scholarly journals Changes in the Ultrastructure of Candida albicans Treated with Cationic Peptides

2020 ◽  
Vol 8 (4) ◽  
pp. 582
Author(s):  
Alina Grigor’eva ◽  
Alevtina Bardasheva ◽  
Anastasiya Tupitsyna ◽  
Nariman Amirkhanov ◽  
Nina Tikunova ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Hyphal Growth ◽  
Antifungal Drugs ◽  
Logarithmic Phase ◽  
Cationic Peptides ◽  
Antifungal Effect ◽  
Morphologic Characteristics ◽  
Transmission Electron ◽  
Wall Ultrastructure ◽  
Ultrathin Sections

Candida albicans is becoming increasingly harmful for humans, which determines the need for new effective antifungal preparations. Currently, when testing antifungals, various morphological methods are used, among which transmission electron microscopy (TEM) is not the leading one. In this work, we used TEM to study the submicroscopic changes in C. albicans cells induced by cationic peptides R9F2 and (KFF)3K. Studies were performed on C. albicans-34 strain from the Collection of EMTC of ICBFM SB RAS in logarithmic phase. R9F2 and (KFF)3K showed an antifungal effect (MIC 10 and 20 μM) and suppressed fungal hyphal growth. Semithin and ultrathin sections of fungal suspensions incubated with 10 μM of peptides were studied at regular intervals from 15 min to 24 h. The first target of both peptides was plasmalemma, and its “alignment” was the only common morphological manifestation of their effect. Other changes in the plasmalemma and alteration of the vacuole and cell wall ultrastructure distinctly differed in cells treated with R9F2 and (KFF)3K peptides. In general, our work has shown pronounced differences of the temporal and morphologic characteristics of the effect of peptides, evidently related to their physicochemical properties. The benefit of TEM studies of ultrathin sections for understanding the mechanisms of action of antifungal drugs is shown.

In vitro and in vivo activity of chelerythrine against Candida albicans and underlying mechanisms

2019 ◽  
Vol 14 (18) ◽  
pp. 1545-1557 ◽  
Author(s):  
Ying Gong ◽  
Siwen Li ◽  
Weixin Wang ◽  
Yiman Li ◽  
Wenli Ma ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Calcium Concentration ◽  
Galleria Mellonella ◽  
Hyphal Growth ◽  
Drug Transporter ◽  
Antifungal Effect ◽  
Underlying Mechanisms

Aim: To evaluate whether chelerythrine (CHT) exhibited antifungal activity against Candida albicans in vitro and in vivo and to explore the underlying mechanisms. Materials & methods: Broth microdilution assay and Galleria mellonella model were used to evaluate the antifungal effect in vitro and in vivo, respectively. Mechanism studies were investigated by morphogenesis observation, Fluo-3/AM, DCFH-DA and rhodamine6G assay, respectively. Results: CHT exhibited antifungal activity against C. albicans and preformed biofilms with minimum inhibitory concentrations ranged from 2 to 16 μg/ml. Besides, CHT protected G. mellonella larvae infected by C. albicans. Mechanisms studies revealed that CHT inhibited hyphal growth, increased intracellular calcium concentration, induced accumulation of reactive oxygen species and inhibited drug transporter activity. Conclusion: CHT exhibited antifungal activity against C. albicans.

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 The vesicle transport protein Vac1p is required for virulence of Candida albicans

Microbiology ◽  
2006 ◽  
Vol 152 (10) ◽  
pp. 3111-3121 ◽  
Author(s):  
Kathrin Franke ◽  
Monika Nguyen ◽  
Albert Härtl ◽  
Hans-Martin Dahse ◽  
Georgia Vogl ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mutant Strain ◽  
Protein Transport ◽  
Systemic Infection ◽  
Hyphal Growth ◽  
Transport Protein ◽  
Vesicle Transport ◽  
Antifungal Drugs ◽  
Null Mutant ◽  
Pathogenic Yeast

The putative vesicle transport protein Vac1p of the human pathogenic yeast Candida albicans plays an important role in virulence. To determine the cellular functions of Vac1p, a null mutant was generated by sequential disruption of both alleles. The vac1 null mutant strain showed defective endosomal vesicle transport, demonstrating a role of Vac1p in protein transport to the vacuole. Vac1p also contributes to resistance to metal ions, as the null mutant strain was hypersensitive to Cu2+, Zn2+ and Ni2+. In addition, the loss of Vac1p affected several virulence factors of C. albicans. In particular, the vac1 null mutant strain showed defective hyphal growth, even when hyphal formation was induced via different pathways. Furthermore, Vac1p affects chlamydospore formation, adherence to human vaginal epithelial cells, and the secretion of aspartyl proteinases (Saps). Avirulence in a mouse model of systemic infection of the vac1 null mutant strongly suggests that Vac1p of C. albicans is essential for pathogenicity. In summary, the Vac1p protein is required for several cellular pathways, in particular those that control virulence and pathogenicity. Consequently, Vac1p is a novel and interesting target for antifungal drugs.

scholarly journals Candida albicans hyphal expansion causes phagosomal membrane damage and luminal alkalinization

2018 ◽  
Author(s):  
Johannes Westman ◽  
Gary Moran ◽  
Selene Mogavero ◽  
Bernhard Hube ◽  
Sergio Grinstein
Keyword(s):  
Candida Albicans ◽  
Fungal Infections ◽  
Membrane Damage ◽  
Hyphal Growth ◽  
Antifungal Drugs ◽  
Apparent Paradox ◽  
Opportunistic Fungi ◽  
Life Threatening ◽  
Proton Leakage ◽  
Phagosomal Membrane

ABSTRACTMacrophages rely on phagosomal acidity to destroy engulfed microorganisms. To survive this hostile response, opportunistic fungi such as Candida albicans developed strategies to evade the acidic environment. C. albicans is polymorphic, able to convert from yeast to hyphae, and this transition is required to subvert the microbicidal activity of the phagosome. However, the phagosomal lumen, which is acidic and nutrient-deprived, inhibits yeast-to-hypha transition. To account for this apparent paradox, it was recently proposed that C. albicans produces ammonia that alkalinizes the phagosome, thus facilitating yeast-to-hypha transformation. We re-examined the mechanism underlying phagosomal alkalinization by applying dual-wavelength ratiometric pH measurements. The phagosomal membrane was found to be highly permeable to ammonia, which is therefore unlikely to account for the pH elevation. Instead, we find that yeast-to-hypha transition begins within acidic phagosomes, and that alkalinization is a consequence of proton leakage induced by excessive membrane distension caused by the expanding hypha.IMPORTANCEC. albicans is the most common nosocomial fungal infection, and over three million people acquire life-threatening invasive fungal infections every year. Even if antifungal drugs exist, almost half of these patients will die. Despite this, fungi remain underestimated as pathogens. Our study uses quantitative biophysical approaches to demonstrate that the yeast-to-hypha transition occurs within the nutrient deprived, acidic phagosome and that alkalinization is a consequence, as opposed to the cause of hyphal growth.

scholarly journals Candida albicans rvs161Δ and rvs167Δ Endocytosis Mutants Are Defective in Invasion into the Oral Cavity

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Shamoon Naseem ◽  
Lois M. Douglas ◽  
James B. Konopka
Keyword(s):  
Candida Albicans ◽  
Environmental Factors ◽  
Oral Cavity ◽  
Fungal Infections ◽  
Hyphal Growth ◽  
Antifungal Drugs ◽  
Invasive Growth ◽  
Oropharyngeal Candidiasis ◽  
Content Type ◽  
Therapeutic Value

ABSTRACT Invasive growth in tissues by the human fungal pathogen Candida albicans is promoted by a switch from budding to hyphal morphogenesis that is stimulated by multiple environmental factors that can vary at different sites of infection. To identify genes that promote invasive growth in the oral cavity to cause oropharyngeal candidiasis (OPC), we first identified C. albicans mutants that failed to invade agar medium. Analysis of nine severely defective mutants in a mouse model of OPC revealed that the strongest defects were seen for the rvs161Δ and rvs167Δ mutants, which lack amphiphysin proteins needed for endocytosis. The rvsΔ mutants initially adhered to the tongue but failed to invade efficiently and were lost from the oral cavity. Previous studies indicated that rvsΔ mutants formed filamentous hyphae in the kidney albeit with morphological abnormalities, suggesting that the rvsΔ mutants were influenced by factors that vary at different sites of infection. Consistent with this, increasing concentrations of CO2, an inducer of hyphal growth that is more abundant in internal organs than air, partially rescued the invasive-growth defects of the rvsΔ mutants in vitro. Interestingly, preinduction of the rvsΔ mutants to form hyphae prior to introduction into the oral cavity restored their ability to cause OPC, identifying a key role for endocytosis in initiating invasive hyphal growth. These results highlight the influence of distinct environmental factors in promoting invasive hyphal growth in the oral cavity and indicate that blocking endocytosis could have therapeutic value in preventing the initiation of OPC. IMPORTANCE Oropharyngeal candidiasis (OPC) is a common fungal infection that is associated with severe morbidity. Another concern is that patients at risk for developing OPC often take long courses of antifungal drugs, which can lead to the emergence of drug-resistant C. albicans strains. We therefore identified nine mutants with defects in undergoing invasive hyphal growth in the oral cavity, increasing the number of genes known to be involved in OPC by more than 30%. The two strongest mutants, rvs161Δ and rvs167Δ, have defects in endocytosis. The rvsΔ mutants appear to have a specific defect in initiating invasive growth, as preinducing the cells to form hyphae prior to infection restored their ability to cause OPC. These results indicate that blocking endocytosis could have therapeutic value in preventing the initiation of OPC without leading to development of resistance against drugs currently used to treat fungal infections.

scholarly journals Antifungal Activity of 3′-Deoxyadenosine (Cordycepin)

1998 ◽  
Vol 42 (6) ◽  
pp. 1424-1427 ◽  
Author(s):  
Alan M. Sugar ◽  
Ronald P. McCaffrey
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Adenosine Deaminase ◽  
Murine Model ◽  
Candida Krusei ◽  
Antifungal Drugs ◽  
Antifungal Effect ◽  
Fluconazole Resistant ◽  
Related Compounds ◽  
Antifungal Efficacy

ABSTRACT The antifungal activity of the nucleoside analog 3′-deoxyadenosine (cordycepin) was studied in a murine model of invasive candidiasis. When protected from deamination by either deoxycoformycin or coformycin, both of which are adenosine deaminase inhibitors, cordycepin exhibited potent antifungal efficacy, as demonstrated by prolongation of survival and a decrease in CFU in the kidneys of mice treated with cordycepin plus an adenosine deaminase inhibitor. The antifungal effect was seen with three different Candidaisolates: Candida albicans 64, a relatively fluconazole-resistant clinical isolate of C. albicans (MIC, 16 μg/ml), and the fluconazole-resistant Candida krusei. Cordycepin and related compounds may provide another avenue for the discovery of clinically useful antifungal drugs.

scholarly journals In Situ Imaging of Candida albicans Hyphal Growth via Atomic Force Microscopy

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Arzu Çolak ◽  
Mélanie A. C. Ikeh ◽  
Clarissa J. Nobile ◽  
Mehmet Z. Baykara
Keyword(s):  
Atomic Force Microscopy ◽  
Candida Albicans ◽  
Adhesion Force ◽  
Hyphal Growth ◽  
Antifungal Drugs ◽  
Content Type ◽  
Force Microscopy ◽  
Atomic Force ◽  
Host Tissues

ABSTRACT Candida albicans is an opportunistic fungal pathogen of humans known for its ability to cause a wide range of infections. One major virulence factor of C. albicans is its ability to form hyphae that can invade host tissues and cause disseminated infections. Here, we introduce a method based on atomic force microscopy to investigate C. albicans hyphae in situ on silicone elastomer substrates, focusing on the effects of temperature and antifungal drugs. Hyphal growth rates differ significantly for measurements performed at different physiologically relevant temperatures. Furthermore, it is found that fluconazole is more effective than caspofungin in suppressing hyphal growth. We also investigate the effects of antifungal drugs on the mechanical properties of hyphal cells. An increase in Young’s modulus and a decrease in adhesion force are observed in hyphal cells subjected to caspofungin treatment. Young’s moduli are not significantly affected following treatment with fluconazole; the adhesion force, however, increases. Overall, our results provide a direct means of observing the effects of environmental factors and antifungal drugs on C. albicans hyphal growth and mechanics with high spatial resolution. IMPORTANCE Candida albicans is one of the most common pathogens of humans. One important virulence factor of C. albicans is its ability to form elongated hyphae that can invade host tissues and cause disseminated infections. Here, we show the effect of different physiologically relevant temperatures and common antifungal drugs on the growth and mechanical properties of C. albicans hyphae using atomic force microscopy. We demonstrate that minor temperature fluctuations within the normal range can have profound effects on hyphal cell growth and that different antifungal drugs impact hyphal cell stiffness and adhesion in different ways.

scholarly journals In Vitro Killing of Candida albicans by Fatty Acids and Monoglycerides

2001 ◽  
Vol 45 (11) ◽  
pp. 3209-3212 ◽  
Author(s):  
Gudmundur Bergsson ◽  
Jóhann Arnfinnsson ◽  
Ólafur Steingrı́msson ◽  
Halldor Thormar
Keyword(s):  
Electron Microscopy ◽  
Fatty Acids ◽  
Transmission Electron Microscopy ◽  
Candida Albicans ◽  
Fatty Acid ◽  
Saturated Fatty Acid ◽  
Capric Acid ◽  
Transmission Electron ◽  
Ultrathin Sections

ABSTRACT The susceptibility of Candida albicans to several fatty acids and their 1-monoglycerides was tested with a short inactivation time, and ultrathin sections were studied by transmission electron microscopy (TEM) after treatment with capric acid. The results show that capric acid, a 10-carbon saturated fatty acid, causes the fastest and most effective killing of all three strains of C. albicans tested, leaving the cytoplasm disorganized and shrunken because of a disrupted or disintegrated plasma membrane. Lauric acid, a 12-carbon saturated fatty acid, was the most active at lower concentrations and after a longer incubation time.

The Ultrastructure of Lymphocytic Hypophysitis

1981 ◽  
Vol 39 ◽  
pp. 466-467
Author(s):  
S.L. Asa ◽  
K. Kovacs ◽  
J. M. Bilbao ◽  
R. G. Josse ◽  
K. Kreines
Keyword(s):  
Electron Microscopy ◽  
Plasma Cells ◽  
Secretory Granules ◽  
Sella Turcica ◽  
Uranyl Acetate ◽  
Lymphocytic Hypophysitis ◽  
Pituitary Cells ◽  
Transmission Electron ◽  
Ultrathin Sections ◽  
Mass Lesions

Seven cases of lymphocytic hypophysitis in women have been reported previously in association with various degrees of hypopituitarism. We report two pregnant patients who presented with mass lesions of the sella turcica, clinically mimicking pituitary adenoma. However, pathologic examination revealed extensive infiltration of the anterior pituitary by lymphocytes and plasma cells with destruction of the gland. To our knowledge, the ultrastructural features of lymphocytic hypophysitis have not been studied so far.For transmission electron microscopy, tissue from surgical specimens was fixed in glutaraldehyde, postfixed in OsO4, dehydrated and embedded in epoxy-resin. Ultrathin sections were stained with uranyl acetate and lead citrate and examined with a Philips 300 electron microscope.Electron microscopy revealed adenohypophysial cells of all types exhibiting varying degrees of injury. In the areas of most dense inflammatory cell infiltration pituitary cells contained large lysosomal bodies fusing with secretory granules (Fig. 1), as well as increased numbers of swollen mitochondria, indicating oncocytic transformation (Fig. 2).

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