scholarly journals (R)-(+)-β-Citronellol and (S)-(−)-β-Citronellol in Combination with Amphotericin B against Candida Spp.

2020 ◽  
Vol 21 (5) ◽  
pp. 1785 ◽  
Author(s):  
Daniele Silva ◽  
Hermes Diniz-Neto ◽  
Laísa Cordeiro ◽  
Maria Silva-Neta ◽  
Shellygton Silva ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Amphotericin B ◽  
Mechanism Of Action ◽  
Inhibitory Concentration ◽  
Association Studies ◽  
Antifungal Drugs ◽  
Candida Spp ◽  
Fungal Cell

The enantiomers (R)-(+)-β-citronellol and (S)-(−)-β-citronellol are present in many medicinal plants, but little is understood about their bioactivity against Candida yeasts. This study aimed to evaluate the behavior of positive and negative enantiomers of β-citronellol on strains of Candida albicans and C. tropicalis involved in candidemia. The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined. The evaluation of growth kinetics, mechanism of action, and association studies with Amphotericin B (AB) using the checkerboard method was also performed. R-(+)-β-citronellol and S-(−)-β-citronellol presented a MIC50% of 64 µg/mL and a MFC50% of 256 µg/mL for C. albicans strains. For C. tropicalis, the isomers exhibited a MIC50% of 256 µg/mL and a MFC50% of 1024 µg/mL. In the mechanism of action assay, both substances displayed an effect on the fungal membrane but not on the fungal cell wall. Synergism and indifference were observed in the association of R-(+)-β-citronellol and AB, while the association between S-(−)-β-citronellol and AB displayed synergism, additivity, and indifference. In conclusion, both isomers of β-citronellol presented a similar profile of antifungal activity. Hence, they can be contemplated in the development of new antifungal drugs providing that further research is conducted about their pharmacology and toxicity.

scholarly journals In vitro activities of Traganum nudatum and Mentha pulegium extracts combined with amphotericin B against Candida albicans in production of hydrolytic enzymes

2020 ◽  
Author(s):  
Ikram Tefiani ◽  
Sidi Mohammed Lahbib Seddiki ◽  
Moustafa Yassine Mahdad
Keyword(s):  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Culture Media ◽  
Hydrolytic Enzymes ◽  
Normal Flora ◽  
Mentha Pulegium ◽  
Hydrolytic Activities

Background and Purpose: Candida albicans is an important microorganism in the normal flora of a healthy subject; however, it has an expedient pathogenic character that induces hydrolytic virulence. Regarding this, the present study aimed to find an in vitro alternative that could reduce the virulence of this yeast. Materials and Methods: For the purpose of the study, the effect of amphotericin B (AmB) combined with the extract of Traganum nudatum (E1) or Mentha pulegium (E2) was evaluated against the hydrolytic activities of esterase, protease, and phospholipase. This effect was determined by calculating the minimum inhibitory concentration (MIC), used to adjust the extract/AmB mixtures in culture media. Results: The evaluated Pz values, which corresponded to the different enzymatic activities, showed a decrease in the hydrolytic activities of C. albicans strains after the addition of E1/AmB and E2/AmB combinations at descending concentrations (lower than the obtained MICs). Conclusion: Based on the findings, it would be possible to reduce the pathogenesis of this species without destabilizing the balance of the flora.

scholarly journals Fluconazole and Lipopeptide Surfactin Interplay During Candida albicans Plasma Membrane and Cell Wall Remodeling Increases Fungal Immune System Exposure

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 314 ◽  
Author(s):  
Jakub Suchodolski ◽  
Daria Derkacz ◽  
Jakub Muraszko ◽  
Jarosław J. Panek ◽  
Aneta Jezierska ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Plasma Membrane ◽  
Immune System ◽  
Antifungal Drugs ◽  
Stable Complex ◽  
Host Immune System ◽  
Chitin Synthesis ◽  
Fungal Cell ◽  
In Silico Studies

Recognizing the β-glucan component of the Candida albicans cell wall is a necessary step involved in host immune system recognition. Compounds that result in exposed β-glucan recognizable to the immune system could be valuable antifungal drugs. Antifungal development is especially important because fungi are becoming increasingly drug resistant. This study demonstrates that lipopeptide, surfactin, unmasks β-glucan when the C. albicans cells lack ergosterol. This observation also holds when ergosterol is depleted by fluconazole. Surfactin does not enhance the effects of local chitin accumulation in the presence of fluconazole. Expression of the CHS3 gene, encoding a gene product resulting in 80% of cellular chitin, is downregulated. C. albicans exposure to fluconazole changes the composition and structure of the fungal plasma membrane. At the same time, the fungal cell wall is altered and remodeled in a way that makes the fungi susceptible to surfactin. In silico studies show that surfactin can form a complex with β-glucan. Surfactin forms a less stable complex with chitin, which in combination with lowering chitin synthesis, could be a second anti-fungal mechanism of action of this lipopeptide.

Comparison of antifungal efficacies of moxifloxacin, liposomal amphotericin B, and combination treatment in experimental Candida albicans endophthalmitis in rabbits

2010 ◽  
Vol 56 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Yudum Tiftikcioğlu Deren ◽  
Şengül Özdek ◽  
Ayşe Kalkanci ◽  
Nalan Akyürek ◽  
Berati Hasanreisoğlu
Keyword(s):  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Amphotericin B ◽  
Combination Treatment ◽  
Liposomal Amphotericin ◽  
Inhibitory Concentration ◽  
Liposomal Amphotericin B ◽  
Control Group

The goal of this study was to compare in vitro and in vivo efficacy of moxifloxacin and liposomal amphotericin B (Amp-B) monotherapies and combination treatment against Candida albicans in an exogenous endophthalmitis model in rabbit eyes. Microplate dilution tests and checkerboard analysis were performed to detect in vitro efficacies. Endophthalmitis was induced by intravitreal injection of C. albicans in 40 rabbit eyes with simultaneous intravitreal drug injection according to prophylactic treatment groups. Group 1 (control group) received 0.1 mL of balanced salt solution, group 2 (moxi group) 100 µg moxifloxacin/0.1 mL, group 3 (Amp-B group) 10 µg liposomal Amp-B/0.1 mL, and group 4 (combi group) both 100 µg moxifloxacin/0.05 mL and 10 µg liposomal Amp-B/0.05 mL intravitreally. Clinical examination, quantitative analysis of microorganisms, and histopathologic examination were performed as in vivo studies. The minimum inhibitory concentration of liposomal Amp-B against C. albicans was found to be 1 µg/mL. Moxifloxacin showed no inhibition of in vitro C. albicans growth. The minimum inhibitory concentration values of liposomal Amp-B for C. albicans were reduced two- to eightfold with increasing concentrations of moxifloxacin in vitro. In vivo, there was no C. albicans growth in the combi group (zero of eight eyes), whereas three eyes (37.5%) showed growth in the Amp-B group. Vitreous inflammation, retinal detachment, focal retinal necrosis, and outer nuclear layer loss were found to be lower in the moxi group compared with the control group. Ganglion cell and inner nuclear layer loss was observed in all eyes (100%) in both the moxi and combi groups, whereas only in 25% (two of eight eyes) in the Amp-B group. Moxifloxacin strongly augments the efficacy of liposomal Amp-B against C. albicans in vitro, although it has no in vitro antifungal activity when used alone. It is interesting that we found a synergistic effect for in vitro tests but failed to demonstrate it in vivo. When 100 µg moxifloxacin/0.1 mL is given intravitreally, it has some toxic effects that are limited to the inner retinal layers.

Interaction of Candida albicans with Fluconazole/ Clotrimazole: Effect on Hyphae Formation and Expression of Hyphal Wall Protein 1

2020 ◽  
Author(s):  
Sakineh Jam Shahriari ◽  
Fahimeh Alizadeh ◽  
Alireza Khodavandi
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Polymerase Chain Reaction Analysis ◽  
Antifungal Drugs ◽  
Opportunistic Human Pathogen ◽  
Hyphal Wall ◽  
Scanning Electron

Background and Aims: Candida albicans (C. albicans) is the most common opportunistic human pathogen. Therapeutic options for Candida infections are limited to available antifungal drugs. The aim of this study was to investigate the effects of fluconazole/clotrimazole (FLU/CLT) on C. albicans hyphae formation. Materials and Methods: We have established the effectiveness of the combination of FLU/CLT on C. albicans hyphae formation. Interaction of C. albicans with combination of FLU/CLT was performed using the CLSI guidelines and time-killing curves. We investigated the anti-hyphal activities of combination of FLU/CLT against C. albicans using XTT and crystal violet assays as well as scanning electron microscopy and expression of HWP1 gene. Results: The interaction of C. albicans with FLU/CLT resulted in synergistic, partial synergistic and indifferent effects. The interaction of FLU/CLT were confirmed by time-killing curves. FLU/CLT combined resulted in the reduction of metabolic activity and hyphae formation in C. albicans. Images taken by scanning electron microscopy indicated the effectiveness on hyphae disruption. According to relative real time polymerase chain reaction analysis, the mean Ct values revealed the significant decrease in expression level of the HWP1 gene. A 2.86- and 2.33-fold decrease in HWP1 gene expression was observed in combination of FLU/CLT treatment at 2× minimum inhibitory concentration and 1× minimum inhibitory concentration, respectively (p=0.002). Conclusions: We confirmed that the hyphae is a target for the combination of FLU/CLT in C. albicans. HWP1 gene is likely to be considered as a probable targets synergistic interaction of FLU/CLT against C. albicans.

scholarly journals Inhibitory Effect of (-)-myrtenol alone and in combination with antifungal agents on Candida spp.

2021 ◽  
Vol 10 (15) ◽  
pp. e35101522434
Author(s):  
Bruno Bezerra Cavalcanti ◽  
Hermes Diniz Neto ◽  
Walicyranison Plinio da Silva-Rocha ◽  
Edeltrudes de Oliveira Lima ◽  
José Maria Barbosa Filho ◽  
...  
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Antifungal Agent ◽  
Antifungal Agents ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Antifungal Drugs ◽  
Additive Effects ◽  
Candida Spp ◽  
Minimum Fungicidal Concentration ◽  
Fungicide Activity

The aim of this study was to examine the effects of (-)-myrtenol alone and combined with antifungal agents against Candida spp. The Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration of (-)-myrtenol and fluconazole against C. albicans and C. parapsilosis strains was obtained using CLSI guidelines. Combination of (-)-myrtenol with antifungal drugs was determined by checkboard test. The (-) myrtenol showed MIC ranging from 256 to 512 µg/mL against both species assay. And the MFC was 512 µg/mL, demonstrated nature fungicidal (MFC/MIC < 4). In addition, combination of antifungal agents (amphotericin B and fluconazole) and (-) myrtenol showed synergistic and additive effects on strains assays. Based on these results, the present study demonstrates that (-) myrtenol showed strong fungicide activity against Candida spp. In addition, Combination of antifungal agents and (-) myrtenol reduces the effective concentrations of both the agents with synergistic to additive effects. Therefore, (-) myrtenol has potential to be developed into an antifungal agent.

scholarly journals Molecular Analysis of the Candida albicans Homolog of Saccharomyces cerevisiae MNN9, Required for Glycosylation of Cell Wall Mannoproteins

1999 ◽  
Vol 181 (24) ◽  
pp. 7439-7448 ◽  
Author(s):  
Susan B. Southard ◽  
Charles A. Specht ◽  
Chitra Mishra ◽  
Joan Chen-Weiner ◽  
Phillips W. Robbins
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Candida Albicans ◽  
Gene Family ◽  
Molecular Analysis ◽  
Transmembrane Domain ◽  
Antifungal Drugs ◽  
Northern Analysis ◽  
Fungal Cell ◽  
Poor Growth

ABSTRACT The fungal cell wall has generated interest as a potential target for developing antifungal drugs, and the genes encoding glucan and chitin in fungal pathogens have been studied to this end. Mannoproteins, the third major component of the cell wall, contain mannose in either O- or N-glycosidic linkages. Here we describe the molecular analysis of the Candida albicans homolog ofSaccharomyces cerevisiae MNN9, a gene required for the synthesis of N-linked outer-chain mannan in yeast, and the phenotypes associated with its disruption. CaMNN9 has significant homology with S. cerevisiae MNN9, including a putative N-terminal transmembrane domain, and represents a member of a similar gene family in Candida. CaMNN9 resides on chromosome 3 and is expressed at similar levels in both yeast and hyphal cells. Disruption of both copies of CaMNN9 leads to phenotypic effects characteristic of cell wall defects including poor growth in liquid media and on solid media, formation of aggregates in liquid culture, osmotic sensitivity, aberrant hyphal formation, and increased sensitivity to lysis after treatment with β-1,3-glucanase. Like all members of the S. cerevisiae MNN9 gene family theCamnn9Δ strain is resistant to sodium orthovanadate and sensitive to hygromycin B. Analysis of cell wall-associated carbohydrates showed the Camnn9Δ strain to contain half the amount of mannan present in cell walls derived from the wild-type parent strain. Reverse transcription-PCR and Northern analysis of the expression of MNN9 gene family members CaVAN1and CaANP1 in the Camnn9Δ strain showed that transcription of those genes is not affected in the absence ofCaMNN9 transcription. Our results suggest that, while the role MNN9 plays in glycosylation in bothCandida and Saccharomyces is conserved, loss ofMNN9 function in C. albicans leads to phenotypes that are inconsistent with the pathogenicity of the organism and thus identify CaMnn9p as a potential drug target.

scholarly journals Liquid and vapor-phase antifungal activities of natural borneol against Candida albicans and its germ tube formation

2021 ◽  
Author(s):  
Yazhou Wang ◽  
Huiling Liu
Keyword(s):  
Candida Albicans ◽  
Minimum Inhibitory Concentration ◽  
Vapor Phase ◽  
Germ Tube ◽  
Inhibitory Concentration ◽  
Antifungal Drugs ◽  
Phase Method ◽  
Dilution Method ◽  
Natural Medicine ◽  
Candida Albicans Infection

AbstractCandida albicans infection mainly occurs in patients with suppressed immune function, and it is also the main pathogen of hospital infection. The new strategies are needed to treat the existing resistance of antifungal drugs. The use of natural products aimed at controlling fungal diseases is considered an interesting alternative to synthetic fungicides due to their lower adverse reactions, lower cost to plant preparations compared to modern conventional pharmaceuticals. Natural borneol has a long history of treating ulcers and local infections. In this study, the minimum inhibitory concentration of natural borneol on ATCC10231 and 10 clinically isolated Candida albicans was determined by vapor phase method and dilution method, and the influence of sub-minimum inhibitory concentration on the formation of Candida albicans hyphae was observed. We found that the minimum inhibitory concentration of ATCC10231 and 10 clinically the isolates in the vapor phase were both 0.4 mg/cm3, agar and broth dilution methods were 2 mg/mL. The vapor phase of natural borneol has a better inhibitory effect on Candida albicans, Sub-mic concentration of borneol (0.125-1mg/ml) in the liquid phase inhibits the 60%-99% formation of Candida albicans germ tube. Natural borneol is a potential natural medicine for the treatment and prevention of Candida albicans infection. It brings new insights into the development of novel effective antifungal drugs.

scholarly journals The Viscoelastic Properties of the Fungal Cell Wall Allow Traffic of AmBisome as Intact Liposome Vesicles

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Louise Walker ◽  
Prashant Sood ◽  
Megan D. Lenardon ◽  
Gillian Milne ◽  
Jon Olson ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Cell Membrane ◽  
Amphotericin B ◽  
Mode Of Action ◽  
Viscoelastic Properties ◽  
Fungal Cell Wall ◽  
Fungal Cell ◽  
Pass Through ◽  
Cell Wall Porosity

ABSTRACT The fungal cell wall is a critically important structure that represents a permeability barrier and protective shield. We probed Candida albicans and Cryptococcus neoformans with liposomes containing amphotericin B (AmBisome), with or without 15-nm colloidal gold particles. The liposomes have a diameter of 60 to 80 nm, and yet their mode of action requires them to penetrate the fungal cell wall to deliver amphotericin B to the cell membrane, where it binds to ergosterol. Surprisingly, using cryofixation techniques with electron microscopy, we observed that the liposomes remained intact during transit through the cell wall of both yeast species, even though the predicted porosity of the cell wall (pore size, ~5.8 nm) is theoretically too small to allow these liposomes to pass through intact. C. albicans mutants with altered cell wall thickness and composition were similar in both their in vitro AmBisome susceptibility and the ability of liposomes to penetrate the cell wall. AmBisome exposed to ergosterol-deficient C. albicans failed to penetrate beyond the mannoprotein-rich outer cell wall layer. Melanization of C. neoformans and the absence of amphotericin B in the liposomes were also associated with a significant reduction in liposome penetration. Therefore, AmBisome can reach cell membranes intact, implying that fungal cell wall viscoelastic properties are permissive to vesicular structures. The fact that AmBisome can transit through chemically diverse cell wall matrices when these liposomes are larger than the theoretical cell wall porosity suggests that the wall is capable of rapid remodeling, which may also be the mechanism for release of extracellular vesicles. IMPORTANCE AmBisome is a broad-spectrum fungicidal antifungal agent in which the hydrophobic polyene antibiotic amphotericin B is packaged within a 60- to 80-nm liposome. The mode of action involves perturbation of the fungal cell membrane by selectively binding to ergosterol, thereby disrupting membrane function. We report that the AmBisome liposome transits through the cell walls of both Candida albicans and Cryptococcus neoformans intact, despite the fact that the liposome is larger than the theoretical cell wall porosity. This implies that the cell wall has deformable, viscoelastic properties that are permissive to transwall vesicular traffic. These observations help explain the low toxicity of AmBisome, which can deliver its payload directly to the cell membrane without unloading the polyene in the cell wall. In addition, these findings suggest that extracellular vesicles may also be able to pass through the cell wall to deliver soluble and membrane-bound effectors and other molecules to the extracellular space.

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