Evaluation of the in-vitro Antifungal Activity of Selected Fungal Species Tested Against Opportunistic Human Pathogen Candida albicans

2020 ◽  
Vol 8 (01) ◽  
pp. 01-08
Author(s):  
Aakriti Shukla ◽  
Apoorva Pathak
Keyword(s):  
Candida Albicans ◽  
Fungal Infections ◽  
Bloodstream Infections ◽  
Fungal Species ◽  
Fungal Metabolites ◽  
Antifungal Antibiotics ◽  
Opportunistic Human Pathogen ◽  
Hospital Acquired ◽  
In Vitro Antifungal Activity

Candida albicans is currently the fourth-leading cause of hospital-acquired bloodstream infections, reaching a mortality rate of up to 35–40% for systemic or disseminated infections. Systemic mycoses can occur in patients with severely impaired immune systems (AIDS), with organ or bone marrow transplants, cancer patients undergoing chemotherapy, and patients in ICU (neonates and elderly). It is, therefore, obvious that there is a substantial need for fast, effective antifungal antibiotics to combat fungal infections. The present investigation has been proposed to screen effective fungal metabolites for the control of Candida albicans by evaluating the potential of fungal bioactive compounds, its purification and characterization

scholarly journals Eap1p, an Adhesin That Mediates Candida albicans Biofilm Formation In Vitro and In Vivo

2007 ◽  
Vol 6 (6) ◽  
pp. 931-939 ◽  
Author(s):  
Fang Li ◽  
Michael J. Svarovsky ◽  
Amy J. Karlsson ◽  
Joel P. Wagner ◽  
Karen Marchillo ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Adhesion ◽  
Biofilm Formation ◽  
Fungal Infections ◽  
Gene Dosage ◽  
Venous Catheter ◽  
Flow Chamber ◽  
Dependent Manner

ABSTRACT Candida albicans is the leading cause of systemic fungal infections in immunocompromised humans. The ability to form biofilms on surfaces in the host or on implanted medical devices enhances C. albicans virulence, leading to antimicrobial resistance and providing a reservoir for infection. Biofilm formation is a complex multicellular process consisting of cell adhesion, cell growth, morphogenic switching between yeast form and filamentous states, and quorum sensing. Here we describe the role of the C. albicans EAP1 gene, which encodes a glycosylphosphatidylinositol-anchored, glucan-cross-linked cell wall protein, in adhesion and biofilm formation in vitro and in vivo. Deleting EAP1 reduced cell adhesion to polystyrene and epithelial cells in a gene dosage-dependent manner. Furthermore, EAP1 expression was required for C. albicans biofilm formation in an in vitro parallel plate flow chamber model and in an in vivo rat central venous catheter model. EAP1 expression was upregulated in biofilm-associated cells in vitro and in vivo. Our results illustrate an association between Eap1p-mediated adhesion and biofilm formation in vitro and in vivo.

scholarly journals Orodispersible Film Loaded with Enterococcus faecium CRL183 Presents Anti-Candida albicans Biofilm Activity In Vitro

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 998
Author(s):  
Virgínia Barreto Lordello ◽  
Andréia Bagliotti Meneguin ◽  
Sarah Raquel de Annunzio ◽  
Maria Pía Taranto ◽  
Marlus Chorilli ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Enterococcus Faecium ◽  
Potato Starch ◽  
Oral Candidiasis ◽  
Candida Spp ◽  
Sem Images ◽  
Control Film ◽  
In Vitro Antifungal Activity

Background: Probiotic bacteria have been emerging as a trustworthy choice for the prevention and treatment of Candida spp. infections. This study aimed to develop and characterize an orodispersible film (ODF) for delivering the potentially probiotic Enterococcus faecium CRL 183 into the oral cavity, evaluating its in vitro antifungal activity against Candida albicans. Methods and Results: The ODF was composed by carboxymethylcellulose, gelatin, and potato starch, and its physical, chemical, and mechanical properties were studied. The probiotic resistance and viability during processing and storage were evaluated as well as its in vitro antifungal activity against C. albicans. The ODFs were thin, resistant, and flexible, with neutral pH and microbiologically safe. The probiotic resisted the ODF obtaining process, demonstrating high viability (>9 log10 CFU·g−1), up to 90 days of storage at room temperature. The Probiotic Film promoted 68.9% of reduction in fungal early biofilm and 91.2% in its mature biofilm compared to the group stimulated with the control film. Those results were confirmed through SEM images. Conclusion: The probiotic ODF developed is a promising strategy to prevent oral candidiasis, since it permits the local probiotic delivery, which in turn was able to reduce C. albicans biofilm formation.

scholarly journals In Vitro Antifungal Activity of (1)-N-2-Methoxybenzyl-1,10-phenanthrolinium Bromide against Candida albicans and Its Effects on Membrane Integrity

Mycobiology ◽  
2017 ◽  
Vol 45 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Setiawati Setiawati ◽  
Titik Nuryastuti ◽  
Ngatidjan Ngatidjan ◽  
Mustofa Mustofa ◽  
Jumina Jumina ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Membrane Integrity ◽  
In Vitro Antifungal Activity

scholarly journals IN SILICO STUDY OF THE ANTIMICROBIAL PROFILE OF β-CITRONELLOL: POTENTIAL AS AN ANTIFUNGAL

2019 ◽  
Vol 16 (32) ◽  
pp. 894-898
Author(s):  
D. F. SILVA ◽  
H. D. NETO ◽  
M. D. L. FERREIRA ◽  
A. A. O. FILHO ◽  
E. O. LIMA
Keyword(s):  
In Silico ◽  
Fungal Infections ◽  
In Silico Analysis ◽  
Fungal Species ◽  
In Silico Study ◽  
Pass Online ◽  
Therapeutic Alternatives ◽  
Bioactivity Profile ◽  
Silico Analysis

β-citronellol (3,7-dimethyl-6-octen-1-ol) has been exhibiting a number of pharmacological effects that creates interest about its antimicrobial potential, since several substances of the monoterpene class have already demonstrated to possess activity in this profile. In addition, the emergence of fungal species resistant to current pharmacotherapy poses a serious challenge to health systems, making it necessary to search for new effective therapeutic alternatives to deal with this problem. In this study, the antimicrobial profile of β-citronellol was analyzed. The Prediction of Activity Spectra for Substances (PASS) online software was used to study the antimicrobial activity of the β-citronellol molecule by the use of in silico analysis. In contrast, an in vitro antifungal study of this monoterpene was carried out. For this purpose, the Minimum Inhibitory Concentration (MIC) was determined by the microdilution technique in 96-well plates in Saboraud Dextrose Broth/RPMI against sensitive strains of Candida albicans, and this assay was performed in duplicate. In the in silico analysis of the antimicrobial profile, it was revealed that the monoterpene β-citronellol had a diverse antimicrobial bioactivity profile. For the antifungal activity, it presented a percentage value with Pa: 58.4% (predominant) and its MIC of 128 μg/mL, which was equivalent for all strains tested. The in silico study of the β-citronellol molecule allowed us to consider that the monoterpenoid is very likely to be bioactive against agents that cause fungal infections.

scholarly journals Expression and Immunostaining Analyses Suggest thatPneumocystisPrimary Homothallism Involves Trophic Cells Displaying Both Plus and Minus Pheromone Receptors

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
A. Luraschi ◽  
S. Richard ◽  
J. M. G. C. F. Almeida ◽  
M. Pagni ◽  
M. T. Cushion ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Severe Pneumonia ◽  
Mate Recognition ◽  
Fungal Species ◽  
Sexual Cycle ◽  
Host Immune System ◽  
Type Locus ◽  
Pheromone Receptor ◽  
Human Lungs

ABSTRACTThe genusPneumocystisencompasses fungal species that colonize mammals’ lungs with host specificity. Should the host immune system weaken, the fungal species can cause severe pneumonia. The life cycle of these pathogens is poorly known, mainly because anin vitroculture method has not been established. Both asexual and sexual cycles would occur. Trophic cells, the predominant forms during infection, could multiply asexually but also enter into a sexual cycle. Comparative genomics revealed a single mating type locus, including plus and minus genes, suggesting that primary homothallism involving self-fertility of each strain is the mode of reproduction ofPneumocystisspecies. We identified and analyzed the expression of themam2andmap3genes encoding the receptors for plus and minus pheromones using reverse transcriptase PCR, in both infected mice and bronchoalveolar lavage fluid samples from patients withPneumocystispneumonia. Both receptors were most often concomitantly expressed during infection, revealing that both pheromone-receptor systems are involved in the sexual cycle. Themap3transcripts were subject to alternative splicing. Using immunostaining, we investigated the presence of the pheromone receptors at the surfaces ofPneumocystiscells from a patient. The staining tools were first assessed inSaccharomyces cerevisiaedisplaying thePneumocystisreceptors at their cellular surface. Both receptors were present at the surfaces of the vast majority of the cells that were likely trophic forms. The receptors might have a role in mate recognition and/or postfertilization events. Their presence at the cell surface might facilitate outbreeding versus inbreeding of self-fertile strains.IMPORTANCEThe fungi belonging to the genusPneumocystismay cause severe pneumonia in immunocompromised humans, a disease that can be fatal if not treated. This disease is nowadays one of the most frequent invasive fungal infections worldwide. Whole-genome sequencing revealed that the sexuality of these fungi involves a single partner that can self-fertilize. Here, we report that two receptors recognizing specifically excreted pheromones are involved in this self-fertility within infected human lungs. Using fluorescent antibodies binding specifically to these receptors, we observed that most often, the fungal cells display both receptors at their surface. These pheromone-receptor systems might play a role in mate recognition and/or postfertilization events. They constitute an integral part of thePneumocystisobligate sexuality within human lungs, a cycle that is necessary for the dissemination of the fungus to new individuals.

scholarly journals Disparate Candida albicans Biofilm Formation in Clinical Lipid Emulsions Due to Capric Acid-Mediated Inhibition

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Hubertine M. E. Willems ◽  
Jeremy S. Stultz ◽  
Molly E. Coltrane ◽  
Jabez P. Fortwendel ◽  
Brian M. Peters
Keyword(s):  
Candida Albicans ◽  
Biofilm Formation ◽  
Bloodstream Infections ◽  
Capric Acid ◽  
Lipid Emulsions ◽  
Biofilm Growth ◽  
Content Type ◽  
Biofilm Model ◽  
Hypha Formation

ABSTRACT Receipt of parenteral nutrition (PN) remains an independent risk factor for developing catheter-related bloodstream infections (CR-BSI) caused by fungi, including by the polymorphic fungus Candida albicans, which is notoriously adept at forming drug-resistant biofilm structures. Among a variety of macronutrients, PN solutions contain lipid emulsions to supply daily essential fats and are often delivered via central venous catheters (CVCs). Therefore, using an in vitro biofilm model system, we sought to determine whether various clinical lipid emulsions differentially impacted biofilm growth in C. albicans. We observed that the lipid emulsions Intralipid and Omegaven both stimulated C. albicans biofilm formation during growth in minimal medium or a macronutrient PN solution. Conversely, Smoflipid inhibited C. albicans biofilm formation by approximately 50%. Follow-up studies revealed that while Smoflipid did not impair C. albicans growth, it did significantly inhibit hypha formation and hyphal elongation. Moreover, growth inhibition could be recapitulated in Intralipid when supplemented with capric acid—a fatty acid present in Smoflipid but absent in Intralipid. Capric acid was also found to dose dependently inhibit C. albicans biofilm formation in PN solutions. This is the first study to directly compare different clinical lipid emulsions for their capacity to affect C. albicans biofilm growth. Results derived from this study necessitate further research regarding different lipid emulsions and rates of fungus-associated CR-BSIs.

scholarly journals Intravital Imaging of Candida albicans Identifies Differential In Vitro and In Vivo Filamentation Phenotypes for Transcription Factor Deletion Mutants

mSphere ◽  
2021 ◽  
Author(s):  
Rohan S. Wakade ◽  
Manning Huang ◽  
Aaron P. Mitchell ◽  
Melanie Wellington ◽  
Damian J. Krysan
Keyword(s):  
Candida Albicans ◽  
Fungal Infections ◽  
Deletion Mutants ◽  
Filamentous Form ◽  
Content Type ◽  
Yeast Form ◽  
Common Causes ◽  
Do So

Candida albicans is one of the most common causes of fungal infections in humans. C. albicans undergoes a transition from a round yeast form to a filamentous form during infection, which is critical for its ability to cause disease. Although this transition has been studied in the laboratory for years, methods to do so in an animal model of infection have been limited.

scholarly journals Deletion of the ATP2 Gene in Candida albicans Blocks Its Escape From Macrophage Clearance

2021 ◽  
Vol 11 ◽  
Author(s):  
Yishan Zhang ◽  
Chuanyan Tang ◽  
Zhanpeng Zhang ◽  
Shuixiu Li ◽  
Yajing Zhao ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Drug Target ◽  
Fungal Infections ◽  
Carbon Sources ◽  
Systemic Infection ◽  
Invasive Infection ◽  
First Line ◽  
Dramatic Decrease

Macrophages provide the first-line defense against invasive fungal infections and, therefore, escape from macrophage becomes the basis for the establishment of Candida albicans invasive infection. Here, we found that deletion of ATP2 (atp2Δ/Δ) in C. albicans resulted in a dramatic decrease from 69.2% (WT) to 1.2% in the escape rate in vitro. The effect of ATP2 on macrophage clearance stands out among the genes currently known to affect clearance. In the normal mice, the atp2Δ/Δ cells were undetectable in major organs 72 h after systemic infection, while WT cells persisted in vivo. However, in the macrophage-depleted mice, atp2Δ/Δ could persist for 72 h at an amount comparable to that at 24 h. Regarding the mechanism, WT cells sustained growth and switched to hyphal form, which was more conducive to escape from macrophages, in media that mimic the glucose-deficient environment in macrophages. In contrast, atp2Δ/Δ cells can remained viable but were unable to complete morphogenesis in these media, resulting in them being trapped within macrophages in the yeast form. Meanwhile, atp2Δ/Δ cells were killed by oxidative stress in alternative carbon sources by 2- to 3-fold more than WT cells. Taken together, ATP2 deletion prevents C. albicans from escaping macrophage clearance, and therefore ATP2 has a functional basis as a drug target that interferes with macrophage clearance.

scholarly journals Evaluation of the in vitro Activity and in vivo Efficacy of Anidulafungin-Loaded Human Serum Albumin Nanoparticles Against Candida albicans

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Zhang ◽  
Yan-Chao Liu ◽  
Si-Min Chen ◽  
Hui Zong ◽  
Wei-Tong Hou ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Water Solubility ◽  
Fungal Infections ◽  
Antifungal Susceptibility ◽  
Fungal Species ◽  
Invasive Infection

Recent decades have seen a significant increase in invasive fungal infections, resulting in unacceptably high mortality rates. Anidulafungin (AN) is the newest echinocandin and appears to have several advantages over existing antifungals. However, its poor water solubility and burdensome route of administration (i.e., repeated, long-term intravenous infusions) have limited its practical use. The objective of this study was to develop anidulafungin-loaded Human Serum Albumin (HSA) nanoparticles (NP) so as to increase both its solubility and antifungal efficacy. HSA was reduced using SDS and DTT, allowing liberation of free thiols to form the intermolecular disulfide network and nanoassembly. Reduced HSA was then added to MES buffer (0.1 M, pH 4.8) and magnetically stirred at 350 rpm and 25°C with AN (m/m 50:1) for 2 h to form nanoparticles (AN NP). We next performed routine antifungal susceptibility testing of Candida strains (n = 31) using Clinical and Laboratory Standards Institute (CLSI) methodologies. Finally, the in vivo efficacy of both AN and AN NP was investigated in a murine model of invasive infection by one of the most common fungal species—C. albicans. The results indicated that our carrier formulations successfully improved the water solubility of AN and encapsulated AN, with the latter having a particle size of 29 ± 1.5 nm with Polymer dispersity index (PDI) equaling 0.173 ± 0.039. In vitro AN NP testing revealed a stronger effect against Candida species (n = 31), with Minimum Inhibitory Concentration (MIC) values 4- to 32-fold lower than AN alone. In mice infected with Candida and having invasive candidiasis, we found that AN NP prolonged survival time (P < 0.005) and reduced fungal burden in kidneys compared to equivalent concentrations of free drug (P < 0.0001). In conclusion, the anidulafungin nanoparticles developed here have the potential to improve drug administration and therapeutic outcomes for individuals suffering from fungal diseases.

The fungal-specific subunit i/j of F1FO-ATP synthase stimulates the pathogenicity of Candida albicans independent of oxidative phosphorylation

2020 ◽  
Author(s):  
Yajing Zhao ◽  
Yan Lyu ◽  
Yanli Zhang ◽  
Shuixiu Li ◽  
Yishan Zhang ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Fungal Infections ◽  
Critical Role ◽  
Antifungal Drug ◽  
F1fo Atp Synthase

Abstract Invasive fungal infections are a major cause of human mortality due in part to a very limited antifungal drug arsenal. The identification of fungal-specific pathogenic mechanisms is considered a crucial step to current antifungal drug development and represents a significant goal to increase the efficacy and reduce host toxicity. Although the overall architecture of F1FO-ATP synthase is largely conserved in both fungi and mammals, the subunit i/j (Su i/j, Atp18) and subunit k (Su k, Atp19) are proteins not found in mammals and specific to fungi. Here, the role of Su i/j and Su k in Candida albicans was characterized by an in vivo assessment of the virulence and in vitro growth and mitochondrial function. Strikingly, the atp18Δ/Δ mutant showed significantly reduced pathogenicity in systemic murine model. However, this substantial defect in infectivity exists without associated defects in mitochondrial oxidative phosphorylation or proliferation in vitro. Analysis of virulence-related traits reveals normal in both mutants, but shows cell wall defects in composition and architecture in the case of atp18Δ/Δ. We also find that the atp18Δ/Δ mutant is more susceptible to attack by macrophages than wild type, which may correlate well with the abnormal cell wall function and increased sensitivity to oxidative stress. In contrast, no significant changes were observed in any of these studies for the atp19Δ/Δ. These results demonstrate that the fungal-specific Su i/j, but not Su k of F1FO-ATP synthase may play a critical role in C. albicans infectivity and represent another opportunity for new therapeutic target investigation. Lay Abstract This study aims to investigate biological functions of fungal-specific subunit i/j and subunit k of ATP synthase in C. albicans oxidative phosphorylation and virulence potential. Our results revealed that subunit i/j, and not subunit k, is critical for C. albicans pathogenicity.

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