scholarly journals The Influence of Cellulose-Type Formulants on Anti-Candida Activity of the Tyrocidines

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 597
Author(s):  
Yasamin Masoudi ◽  
Wilma van Rensburg ◽  
Bernice Barnard-Jenkins ◽  
Marina Rautenbach
Keyword(s):  
Environmental Changes ◽  
Methyl Cellulose ◽  
Antifungal Drugs ◽  
Haemolytic Activity ◽  
Synergistic Activity ◽  
Phenotypic Flexibility ◽  
Defence Mechanisms ◽  
Candida Spp ◽  
Order Structures ◽  
Topical Applications

Candida species are highly adaptable to environmental changes with their phenotypic flexibility allowing for the evasion of most host defence mechanisms. Moreover, increasing resistance of human pathogenic Candida strains has been reported against all four classes of available antifungal drugs, which highlights the need for combinational therapies. Tyrocidines are cyclic antimicrobial peptides that have shown synergistic activity with antifungal drugs such as caspofungin and amphotericin B. However, these cyclodecapeptides have haemolytic activity and cytotoxicity, but they have been used for decades in the clinic for topical applications. The tyrocidines tend to form higher-order structures in aqueous solutions and excessive aggregation can result in variable or diminished activity. Previous studies have shown that the tyrocidines prefer ordered association to celluloses. Therefore, a formulation with soluble cellulose was used to control the oligomer stability and size, thereby increasing the activity against Candida spp. Of the formulants tested, it was found that commercial hydroxy-propyl-methyl cellulose, E10M, yielded the best results with increased stability, increased anti-Candida activity, and improved selectivity. This formulation holds promise in topical applications against Candida spp. infections.

Effects of calcineurin inhibitors, cyclosporine A and tacrolimus (FK506), on the activity of antifungal drugs against Candida spp.

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Sümeyye Şen Kaya ◽  
Nuri Kiraz ◽  
Ayşe Bariş ◽  
Deniz Turan ◽  
Yasemin Öz ◽  
...  
Keyword(s):  
Cyclosporine A ◽  
Fungal Infections ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Antifungal Drugs ◽  
Synergistic Activity ◽  
Candida Spp ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Time Kill

Introduction. The simultaneous use of antifungals with immunosuppressive agents has become a necessity for patients taking immunosuppressive therapy. However, antifungal drugs are problematic because of their limited target. Hypothesis. Scientists have been searching for new antifungals and some compounds with at least additive effects on antifungals. Calcineurin inhibitors used as immunosuppressive agents also attract attention due to their antifungal property. Aim. To evaluate the activity of two calcineurin inhibitors alone and in combination with amphotericin B (AMB), caspofungin (CAS), itraconazole (ITR), voriconazole (VOR) and fluconazole (FLU). Methodology. MICs of AMB, CAS, ITR, VOR, FLU and cyclosporine A (CsA) and tacrolimus (TAC) as calcineurin inhibitors were evaluated by the broth microdilution method against Candida albicans (n=13), C. krusei (n=7) and C. glabrata (n=10). Checkerboard and time-kill methods were performed to investigate the activity of combining calcineurin inhibitors with antifungal drugs. Results. The lowest MIC values were detected with VOR for all Candida isolates tested. Although we did not detect any inhibition for CsA or TAC alone at concentrations tested in this study, the combinations of CAS with CsA showed the highest synergistic activity (36.7%) by the checkerboard method, and CAS with CsA and ITR with TAC combinations exhibited apparent synergistic interaction by the time-kill method. However, the combinations of both CsA and TAC with AMB resulted in antagonistic interactions, especially against C. krusei isolate in time-kill testing. Conclusion. Synergistic interactions in the combinations of TAC or CsA with antifungal drugs, except for AMB, in many concentrations was found to be promising in terms of the treatment of patients with fungal infections.

Opportunistic yeast pathogen Candida spp.: Secreted and membrane-bound virulence factors

2021 ◽  
Author(s):  
Si Jie Lim ◽  
Mohd Shukuri Mohamad Ali ◽  
Suriana Sabri ◽  
Noor Dina Muhd Noor ◽  
Abu Bakar Salleh ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Drug Targets ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Host Immune System ◽  
Structural Studies ◽  
Candida Spp ◽  
Structural Investigations ◽  
Membrane Bound ◽  
Aspartyl Proteinases

Abstract Candidiasis is a fungal infection caused by Candida spp. especially Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis. Although the medicinal therapeutic strategies have rapidly improved, the mortality rate due to candidiasis has continuously increased. The secreted and membrane-bound virulence factors (VFs) are responsible for fungal invasion, damage and translocation through the host enterocytes besides the evasion from host immune system. VFs such as agglutinin-like sequences (Als), heat shock protein 70, phospholipases, secreted aspartyl proteinases (Sap), lipases, enolases and phytases are mostly hydrolases which degrade the enterocyte membrane components except for candidalysin, the VF acts as a peptide toxin to induce necrotic cell lysis. To date, structural studies of the VFs remain underexplored, hindering their functional analyses. Among the VFs, only secreted aspartyl proteinases and agglutinin-like sequences have their structures deposited in Protein Data Bank (PDB). Therefore, this review scrutinizes the mechanisms of these VFs by discussing the VF-deficient studies of several Candida spp. and their abilities to produce these VFs. Nonetheless, their latest reported sequential and structural analyses are discussed to impart a wider perception of the host-pathogen interactions and potential vaccine or antifungal drug targets. This review signifies that more VFs structural investigations and mining in the emerging Candida spp. are required to decipher their pathogenicity and virulence mechanisms compared to the prominent C. albicans. Lay Abstract Candida virulence factors (VFs) including mainly enzymes and proteins play vital roles in breaching the human intestinal barrier and causing deadly candidiasis. Limited VFs’ structural studies hinder deeper comprehension of their mechanisms and thus the design of vaccines and antifungal drugs against fungal infections.

Essential oils as alternative promising anti-Candidal agents: progress and prospects

2021 ◽  
Vol 27 ◽  
Author(s):  
Awad Shala ◽  
Shweta Singh ◽  
Saif Hameed ◽  
.M.P. Khurana
Keyword(s):  
Essential Oils ◽  
Antioxidant Properties ◽  
Therapeutic Agents ◽  
Antifungal Drugs ◽  
Fungal Resistance ◽  
Antifungal Compounds ◽  
Candida Spp ◽  
Conventional Antibiotics ◽  
Opportunistic Pathogenic

: Candida albicans is one of the main agents responsible for opportunistic pathogenic infections. The progressive emergence of fungal resistance to conventional antibiotics and its side effects as well as treatment costs are considered as major limitations for antifungal drugs. It has drawn scientists' attention to search for potential substitution and therapeutic reliable alternatives for the antifungal compounds from sources like medicinal plants, which contain numerous bioactive compounds such as essential oils. Essential oils (EO) apart from having lower toxicity and better biodegradability are eco-friendly in nature as compared with conventional antibiotics. Furthermore, extracted essential oils have been reported to possess potent antimicrobial, anti-inflammatory and antioxidant properties that nominate them as natural promising candidates to combat numerous fungal ailments. Thus, determination of antifungal efficacy of essential oil-bearing plants on Candida spp. will provide miscellaneous knowledge for future clinical studies that are required for development of new formulations as alternative therapeutic agents to control the growth of Candida species. Therefore, this review summarizes the gist of major essential oils that have been investigated for their anti- Candida potential with some recommendations for further study.

scholarly journals Susceptibility Pattern of Caspofungin-Coated Gold Nanoparticles against Clinically Important Candida Species

2020 ◽  
Author(s):  
Zahra Salehi ◽  
Azam Fattahi ◽  
Ensieh lotfali ◽  
Abdolhassan Kazemi ◽  
Ali Shakeri-Zadeh ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Gold Nanoparticles ◽  
Cell Wall ◽  
Candida Species ◽  
Spherical Shape ◽  
Sem Analysis ◽  
Antifungal Drugs ◽  
Wall Structure ◽  
Candida Spp ◽  
Average Size

Purpose: The present study was performed to examine whether caspofungin-coated gold nanoparticles (CAS-AuNPs) may offer the right platform for sensitivity induction in resistant isolates. Methods: For the purpose of the study, a total of 58 archived Candida species were enrolled in the research. The identification of Candida spp. was performed using polymerase chain reaction-restriction fragment length polymorphism and HWP1 gene amplification approaches. The conjugated CAS-AuNPs were synthesized and then characterized using transmission electron microscopy (TEM) and Zetasizer system to determine their morphology, size, and charge. Furthermore, the efficacy of CAS, CAS-AuNPs conjugate, and AuNPs against Candida spp. was assessed based on the Clinical and Laboratory Standards Institute M60. Finally, the interaction of CAS-AuNPs with Candida element was evaluated via scanning electron microscopy (SEM). Results: According to the TEM results, the synthesized CAS-AuNPs had a spherical shape with an average size of 20 nm. The Zeta potential of CAS-AuNPs was -38.2 mV. Statistical analyses showed that CAS-AuNPs could significantly reduce the minimum inhibitory concentration against C. albicans (P=0.0005) and non-albicans Candida (NAC) species (P<0.0001). All isolates had a MIC value of ≥ 4 µg/ml for CAS, except for C. glabrata. The results of SEM analysis confirmed the effects of AuNPs on the membrane and cell wall structure of C. globrata exposed to CAS-AuNPs, facilitating the formation of pores on the cell wall and finally cell death. Conclusion: The findings revealed that CAS-AuNPs conjugates had significant antifungal effects against Candida spp. through the degradation of the membrane and cell wall integrity. Therefore, it can be concluded that the encapsulation of antifungal drugs in combination with NPs not only diminishes side effects but also enhances the effectiveness of the medications.

scholarly journals The Epidemiological Profile of Candidemia at an Indian Trauma Care Center

2014 ◽  
Vol 6 (02) ◽  
pp. 096-101 ◽  
Author(s):  
Vibhor Tak ◽  
Purva Mathur ◽  
Prince Varghese ◽  
Jacinta Gunjiyal ◽  
Immaculata Xess ◽  
...  
Keyword(s):  
Antifungal Susceptibility ◽  
Fatal Outcome ◽  
Antifungal Drugs ◽  
Identification System ◽  
Trauma Patients ◽  
Candida Spp ◽  
Tetrazolium Chloride ◽  
Blood Samples ◽  
Hospital Infection Control ◽  
Vitek 2

ABSTRACT Purpose: Candida spp. is a common cause of bloodstream infections. Candidemia is a potentially fatal infection that needs urgent intervention to salvage the patients. Trauma patients are relatively young individuals with very few comorbidities, and the epidemiology of candidemia is relatively unknown in this vulnerable and growing population. In this study, we report the epidemiology of candidemia in a tertiary care Trauma Center of India. Materials and Methods: The study was conducted from January 2009 to July 2012. All patients from whose blood samples a Candida spp. was recovered were included in this study. A detailed history and follow up of the patients was done. The isolates of Candida were identified to the species level. The speciation was done by conventional methods, including morphology on Corn Meal Agar, color development on Triphenyl Tetrazolium Chloride Agar and CHROMagar, and germ tube tests. The VITEK 2 YST ID colorometric card, a fully automated identification system was also used. Antifungal susceptibility was performed using the VITEK 2 system. Results: A total of 212 isolates of the Candida species were recovered from blood samples of 157 patients over the study period. Candida tropicalis, 82 (39%), was the most common, followed by C. parapsilosis, 43 (20%), C. albicans, 29 (14%), C. glabrata, 24 (11%), C. rugosa, 20 (9%), C. hemulonii,; 6 (3%), C. guilliermondii, 4 (2%), C. famata, 3 (1.5%), and C. lusitaniae 1 (0.5%). Out of all the candidemia patients, 68 (43%) had a fatal outcome. Fluconazole and Amphotericin B resistance was seen in seven (3.3%) and seven (3.3%) of the isolates, respectively. Conclusion: Candidemia is a significant cause of mortality in trauma patients in our center, with C. tropicalis and C. parapsilosis being the predominant pathogens. Resistance to antifungal drugs is a matter of concern. Better hospital infection control practices and good antibiotic stewardship policies could possibly help in reducing the morbidity and mortality associated with candidemia.

scholarly journals Molecules and Metabolites from Natural Products as Inhibitors of Biofilm in Candida spp. pathogens

2019 ◽  
Vol 19 (28) ◽  
pp. 2567-2578 ◽  
Author(s):  
Rajeev K. Singla ◽  
Ashok K. Dubey
Keyword(s):  
Natural Products ◽  
Mechanism Of Action ◽  
Functional Characterization ◽  
Streptococcus Thermophilus ◽  
Antifungal Drugs ◽  
Bioactive Molecules ◽  
Review Of The Literature ◽  
Candida Spp ◽  
Biofilm Inhibition

Background: Biofilm is a critical virulence factor associated with the strains of Candida spp. pathogens as it confers significant resistance to the pathogen against antifungal drugs. Methods: A systematic review of the literature was undertaken by focusing on natural products, which have been reported to inhibit biofilms produced by Candida spp. The databases explored were from PubMed and Google Scholar. The abstracts and full text of the manuscripts from the literature were analyzed and included if found significant. Results: Medicinal plants from the order Lamiales, Apiales, Asterales, Myrtales, Sapindales, Acorales, Poales and Laurales were reported to inhibit the biofilms formed by Candida spp. From the microbiological sources, lactobacilli, Streptomyces chrestomyceticus and Streptococcus thermophilus B had shown the strong biofilm inhibition potential. Further, the diverse nature of the compounds from classes like terpenoids, phenylpropanoid, alkaloids, flavonoids, polyphenol, naphthoquinone and saponin was found to be significant in inhibiting the biofilm of Candida spp. Conclusion: Natural products from both plant and microbial origins have proven themselves as a goldmine for isolating the potential biofilm inhibitors with a specific or multi-locus mechanism of action. Structural and functional characterization of the bioactive molecules from active extracts should be the next line of approach along with the thorough exploration of the mechanism of action for the already identified bioactive molecules.

scholarly journals Modulatory antimicrobial activity of piper arboreum extracts

2014 ◽  
Vol 73 (1) ◽  
pp. 303-311 ◽  
Author(s):  
Saulo R. Tintino ◽  
Celestina E. S. Souza ◽  
Gláucia M. M. Guedes ◽  
Jaqueline I. V. Costa ◽  
Francisco M. Duarte ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Natural Products ◽  
Ethanol Extract ◽  
Antifungal Drugs ◽  
Synergistic Activity ◽  
Sexually Transmitted ◽  
Microdilution Method ◽  
Antibiotic Drugs ◽  
Pharmacological Targets ◽  
Microbial Infections

AbstractThe side effects of certain antibiotics have been a recent dilemma in the medical arena. Due this fact, the necessity of natural product discovery could provide important indications against several pharmacological targets and combat many infectious agents. Piper arboreum Aub. (Piperaceae) has been used by Brazilian traditional communities against several illnesses including rheumatism, bronchitis, sexually transmitted diseases and complaints of the urinary tract. Medicinal plants are a source of several remedies used in clinical practice to combat microbial infections. In this study, ethanol extract and fractions of Piper arboreum leaves were used to assay antimicrobial and modulatory activity. The minimum inhibitory concentration (MIC) was determined using microdilution method of ethanol extract and fractions from the leaves of P. arboreum ranging between 8 and 1024 μg mL-1. The capacity of these natural products to enhance the activity of antibiotic and antifungal drugs was also assayed. In these tests, natural products were combined with drugs. The natural products assayed did not demonstrate any clinically relevant antimicrobial activity (MIC ≥ 1024 μg mL-1). However, the modulation of antibiotic activity assay observed a synergistic activity of natural products combined with antifungal (such as nystatin and amphotericin B) and antibiotic drugs (such as amikacin, gentamicin and kanamycin). According to these results, these natural products can be an interesting alternative not only to combat infectious diseases caused by bacteria or fungi, but also to combat enhanced resistance of microorganisms to antibiotic and antifungal drugs.

Octyl gallate triggers dysfunctional mitochondria leading to ROS driven membrane damage and metabolic inflexibility along with attenuated virulence in Candida albicans

2019 ◽  
Vol 58 (3) ◽  
pp. 380-392 ◽  
Author(s):  
Venkata Saibabu ◽  
Zeeshan Fatima ◽  
Kamal Ahmad ◽  
Luqman Ahmad Khan ◽  
Saif Hameed
Keyword(s):  
Candida Albicans ◽  
Isocitrate Lyase ◽  
Membrane Damage ◽  
Carbon Sources ◽  
Antifungal Drugs ◽  
In Vivo Studies ◽  
Haemolytic Activity ◽  
Metabolic Inflexibility ◽  
Underlying Mechanisms

Abstract Recently the high incidence of worldwide Candida infections has substantially increased. The growing problem about toxicity of antifungal drugs and multidrug resistance aggravates the need for the development of new effective strategies. Natural compounds in this context represent promising alternatives having potential to be exploited for improving human health. The present study was therefore designed to evaluate the antifungal effect of a naturally occurring phenolic, octyl gallate (OG), on Candida albicans and to investigate the underlying mechanisms involved. We demonstrated that OG at 25 μg/ml could effectively inhibit C. albicans. Mechanistic insights revealed that OG affects mitochondrial functioning as Candida cells exposed to OG did not grow on non-fermentable carbon sources. Dysfunctional mitochondria triggered generation of reactive oxygen species (ROS), which led to membrane damage mediated by lipid peroxidation. We explored that OG inhibited glucose-induced reduction in external pH and causes decrement in ergosterol levels by 45%. Furthermore, OG impedes the metabolic flexibility of C. albicans by inhibiting the glyoxylate enzyme isocitrate lyase, which was also confirmed by docking analysis. Additionally, OG affected virulence traits such as morphological transition and cell adherence. Furthermore, we depicted that OG not only prevented biofilm formation but eliminates the preformed biofilms. In vivo studies with Caenorhabditis elegans nematode model confirmed that OG could enhance the survival of C. elegans after infection with Candida. Toxicity assay using red blood cells showed only 27.5% haemolytic activity. Taken together, OG is a potent inhibitor of C. albicans that warrants further structural optimization and pharmacological investigations.

scholarly journals COVID-19-Associated Candidiasis (CAC): An Underestimated Complication in the Absence of Immunological Predispositions?

2020 ◽  
Vol 6 (4) ◽  
pp. 211 ◽  
Author(s):  
Amir Arastehfar ◽  
Agostinho Carvalho ◽  
M. Hong Nguyen ◽  
Mohammad Taghi Hedayati ◽  
Mihai G. Netea ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Molecular Techniques ◽  
Antifungal Drugs ◽  
Diagnostic Tools ◽  
Candida Spp ◽  
Comparative Performance ◽  
Number Of Patients ◽  
Clinical Awareness

The recent global pandemic of COVID-19 has predisposed a relatively high number of patients to acute respiratory distress syndrome (ARDS), which carries a risk of developing super-infections. Candida species are major constituents of the human mycobiome and the main cause of invasive fungal infections, with a high mortality rate. Invasive yeast infections (IYIs) are increasingly recognized as s complication of severe COVID-19. Despite the marked immune dysregulation in COVID-19, no prominent defects have been reported in immune cells that are critically required for immunity to Candida. This suggests that relevant clinical factors, including prolonged ICU stays, central venous catheters, and broad-spectrum antibiotic use, may be key factors causing COVID-19 patients to develop IYIs. Although data on the comparative performance of diagnostic tools are often lacking in COVID-19 patients, a combination of serological and molecular techniques may present a promising option for the identification of IYIs. Clinical awareness and screening are needed, as IYIs are difficult to diagnose, particularly in the setting of severe COVID-19. Echinocandins and azoles are the primary antifungal used to treat IYIs, yet the therapeutic failures exerted by multidrug-resistant Candida spp. such as C. auris and C. glabrata call for the development of new antifungal drugs with novel mechanisms of action.

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