scholarly journals Antifungal Polymeric Materials and Nanocomposites

2021 ◽  
Vol 9 ◽  
Author(s):  
Winnie Ntow-Boahene ◽  
David Cook ◽  
Liam Good
Keyword(s):  
Cell Membrane ◽  
Small Molecule ◽  
Plant Pathogens ◽  
Fungal Infections ◽  
Synergistic Effects ◽  
Polymeric Materials ◽  
Antifungal Drugs ◽  
Candida Spp ◽  
Fungal Cell ◽  
Antimicrobial Polymers

Rising global populations due to medicinal advancements increases the patient population susceptible to superficial and severe fungal infections. Fungi often implicated in these diseases includes the dermatophytes (Microsporum spp., Epidermophtyon spp., Trichophyton spp.) as well as species of the Candida spp., Aspergillosis spp. and Cryptococcus spp. genera. In addition, increasing global populations leads to increasing agricultural demands. Thus, fungal infections of preharvested crops and stored food by plant pathogens such as Magnaporthe oryzae and Fusarium oxysporum can have detrimental socioeconomic effects due to food insecurity. Current antifungal strategies are based mainly on small molecule antifungal drugs. However, these drugs are limited by poor solubility and bioavailability. Furthermore, antifungal resistance against these drugs are on the rise. Thus, antimicrobial polymers offer an alternative antifungal strategy. Antifungal polymers are characterised by cationic and hydrophobic regions where the cationic regions have been shown to interact with microbial phospholipids and membranes. These polymers can be synthetic or natural and demonstrate distinct antifungal mechanisms ranging from fungal cell membrane permeabilisation, cell membrane depolarisation or cell entry. Although the relative importance of such mechanisms is difficult to decipher. Due to the chemical properties of these polymers, they can be combined with other antimicrobial compounds including existing antifungal drugs, charcoals, lipids and metal ions to elicit synergistic effects. In some cases, antifungal polymers and nanocomposites show better antifungal effects or reduced toxicity compared to the widely used small molecule antifungal drugs. This review provides an overview of antimicrobial polymers and nanocomposites with antifungal activity and the current understanding of their antifungal mechanisms.

scholarly journals Antibiotics in Combination with Antifungals to Combat Drug Resistant Candida – A Concept on Drug Repurposing

2020 ◽  
pp. 42-48
Author(s):  
Hannah Monalis ◽  
R. Sujith ◽  
K. V. Leela ◽  
V. Balamurali
Keyword(s):  
Drug Resistance ◽  
Invasive Candidiasis ◽  
Fungal Infections ◽  
Synergistic Effects ◽  
Experimental Studies ◽  
Drug Repurposing ◽  
Antifungal Drugs ◽  
Dilution Method ◽  
Drug Resistant ◽  
Candida Spp

Candida spp. are emerging pathogens of hospital-acquired infections that causes invasive candidiasis, leading to human mortality and morbidity. Evolution of resistance to different groups of antifungal drugs is a major concern nowadays. Resistance mechanism in some of the antifungal drugs are formation of biofilms, alterations in drug target and lowered intracellular drug levels caused by efflux pumps. Introduction of novel strategies are necessitous to eliminate the phenomenon of drug resistance.  Drug repurposing is a promising therapeutic strategy that can improve the efficacy of antifungal therapy for invasive candidiasis. Antibiotics and antifungal drugs were combined against resistant Candida spp. and the in vitro antifungal synergy were analyzed by disk diffusion methods, checkerboard microbroth dilution method and time-kill curves. Synergistic effects were seen against drug-resistant strains, but drug-susceptible strains show indifferent effects in experimental studies. Profiting from the synergistic effects of combination therapy, alternative therapeutic approaches for drug resistance could be designed. This review will discuss different antifungal drugs and their mechanism, drug-resistance mechanisms and some of the antibiotic and antifungal combinations that provide novel insights in treating invasive 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.

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.

scholarly journals The Chitin Connection

mBio ◽  
2012 ◽  
Vol 3 (2) ◽  
Author(s):  
David L. Goldman ◽  
Alfin G. Vicencio
Keyword(s):  
Cell Wall ◽  
Cell Membrane ◽  
Fungal Infections ◽  
Allergic Inflammation ◽  
Chitinase Activity ◽  
Chitin Deacetylase ◽  
Fungal Cell ◽  
Content Type ◽  
Covalently Linked

ABSTRACTChitin, a polymer ofN-acetylglucosamine, is an essential component of the fungal cell wall. Chitosan, a deacetylated form of chitin, is also important in maintaining cell wall integrity and is essential forCryptococcus neoformansvirulence. In their article, Gilbert et al. [N. M. Gilbert, L. G. Baker, C. A. Specht, and J. K. Lodge, mBio 3(1):e00007-12, 2012] demonstrate that the enzyme responsible for chitosan synthesis, chitin deacetylase (CDA), is differentially attached to the cell membrane and wall. Bioactivity is localized to the cell membrane, where it is covalently linked via a glycosylphosphatidylinositol (GPI) anchor. Findings from this study significantly enhance our understanding of cryptococcal cell wall biology. Besides the role of chitin in supporting structural stability, chitin and host enzymes with chitinase activity have an important role in host defense and modifying the inflammatory response. Thus, chitin appears to provide a link between the fungus and host that involves both innate and adaptive immune responses. Recently, there has been increased attention to the role of chitinases in the pathogenesis of allergic inflammation, especially asthma. We review these findings and explore the possible connection between fungal infections, the induction of chitinases, and asthma.

scholarly journals Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species

2009 ◽  
Vol 58 (11) ◽  
pp. 1454-1462 ◽  
Author(s):  
Eugénia Pinto ◽  
Luís Vale-Silva ◽  
Carlos Cavaleiro ◽  
Lígia Salgueiro
Keyword(s):  
Antifungal Activity ◽  
Essential Oil ◽  
Cell Membrane ◽  
Fungal Infections ◽  
Yeast Cells ◽  
Syzygium Aromaticum ◽  
Clove Oil ◽  
Fungal Cell ◽  
Minimum Fungicidal Concentration ◽  
Clove Essential Oil

The composition and antifungal activity of clove essential oil (EO), obtained from Syzygium aromaticum, were studied. Clove oil was obtained commercially and analysed by GC and GC-MS. The EO analysed showed a high content of eugenol (85.3 %). MICs, determined according to Clinical and Laboratory Standards Institute protocols, and minimum fungicidal concentration were used to evaluate the antifungal activity of the clove oil and its main component, eugenol, against Candida, Aspergillus and dermatophyte clinical and American Type Culture Collection strains. The EO and eugenol showed inhibitory activity against all the tested strains. To clarify its mechanism of action on yeasts and filamentous fungi, flow cytometric and inhibition of ergosterol synthesis studies were performed. Propidium iodide rapidly penetrated the majority of the yeast cells when the cells were treated with concentrations just over the MICs, meaning that the fungicidal effect resulted from an extensive lesion of the cell membrane. Clove oil and eugenol also caused a considerable reduction in the quantity of ergosterol, a specific fungal cell membrane component. Germ tube formation by Candida albicans was completely or almost completely inhibited by oil and eugenol concentrations below the MIC values. The present study indicates that clove oil and eugenol have considerable antifungal activity against clinically relevant fungi, including fluconazole-resistant strains, deserving further investigation for clinical application in the treatment of fungal infections.

scholarly journals Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Visesato Mor ◽  
Antonella Rella ◽  
Amir M. Farnoud ◽  
Ashutosh Singh ◽  
Mansa Munshi ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Sequencing Analysis ◽  
Fungal Cell ◽  
New Class ◽  
Narrow Spectrum

ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. IMPORTANCE Fungal infections are a significant cause of morbidity and mortality worldwide. Current antifungal drugs suffer from various drawbacks, including toxicity, drug resistance, and narrow spectrum of activity. In this study, we have demonstrated that pharmaceutical inhibition of fungal glucosylceramide presents a new opportunity to treat cryptococcosis and various other fungal infections. In addition to being effective against pathogenic fungi, the compounds discovered in this study were well tolerated by animals and additive to current antifungals. These findings suggest that these drugs might pave the way for the development of a new class of antifungals.

scholarly journals Prevalence and Fluconazole Susceptibility Profile of Candida spp. Clinical Isolates in a Brazilian Tertiary Hospital in Minas Gerais, Brazil

2015 ◽  
Vol 87 (2 suppl) ◽  
pp. 1349-1359 ◽  
Author(s):  
Athayde Neves-Junior ◽  
Ana Carolina Cartágenes-Pinto ◽  
Débora A.S. Rocha ◽  
Leandro F. Reis de Sá ◽  
Maria de Lourdes Junqueira ◽  
...  
Keyword(s):  
Opportunistic Infections ◽  
Fungal Infections ◽  
Tertiary Hospital ◽  
Antifungal Drugs ◽  
Control Measures ◽  
Clinical Isolates ◽  
University Hospital ◽  
Effective Control ◽  
Candida Spp ◽  
Resistance Phenotype

Candidiasis has become an important concern for clinical practice, especially with the increasing incidence of immunocompromised patients. In this scenario, the development resistance to fluconazole presents a challenge for treating these opportunistic infections. The aim of this study was to evaluate some epidemiology features of Candidainfections in a Brazilian University Hospital using data, previously unavailable. We observed that 44% of the 93 clinical isolates tested, belonged to Candida albicansspecies and 56% belonged to non-Candida albicansspecies (mainly Candida tropicalis and Candida glabrata). Most strains were isolated from urine samples where C. albicans was predominantly detected. 29 strains presented a fluconazole resistance phenotype and of these, 22 were chemosensitised by FK506, a classical inhibitor of ABC transporters related to azoles resistance. These data suggest the probable role of efflux pumps in this resistance phenotype. Our study highlights the need for developing effective control measures for fungal infections, rational use of antifungal drugs and development of new molecules able to abrogate the active transport of antifungals.

Organic Antifungal Drugs and Targets of Their Action

2021 ◽  
Vol 21 ◽  
Author(s):  
Alexander Yu. Maksimov ◽  
Svetlana Yu. Balandina ◽  
Pavel A. Topanov ◽  
Irina V. Mashevskaya ◽  
Sandeep Chaudhary
Keyword(s):  
Molecular Design ◽  
Fungal Infections ◽  
Wide Spectrum ◽  
Molecular Targets ◽  
Antifungal Drugs ◽  
The Body ◽  
Fungal Diseases ◽  
Fungal Cell ◽  
Genomics And Proteomics

: In recent decades, there has been a significant increase in the number of fungal diseases. This is due to a wide spectrum of action, immunosuppressants and other group drugs. In terms of frequency, rapid spread and globality, fungal infections are approaching acute respiratory infections. Antimycotics are medicinal substances endorsed with fungicidal or fungistatic properties. For the treatment of fungal diseases, several groups of compounds are used that differ in their origin (natural or synthetic), molecular targets and mechanism of action, antifungal effect (fungicidal or fungistatic), indications for use (local or systemic infections), methods of administration (parenteral, oral, outdoor). Several efforts have been made by various medicinal chemists around the world for the development of antifungal drugs with high efficacy with least toxicity and maximum selectivity in the area of antifungal chemotherapy. The pharmacokinetic properties of the new antimycotics are also important: the ability to penetrate biological barriers, be absorbed and distributed in tissues and organs, get accumulated in tissues affected by micromycetes, drug metabolism in the intestinal microflora and human organs, and in the kinetics of excretion from the body. There are several ways to search for new effective antimycotics: - Obtaining new derivatives of the already used classes of antimycotics with improved activity properties. - Screening of new chemical classes of synthetic antimycotic compounds. - Screening of natural compounds. - Identification of new unique molecular targets in the fungal cell. - Development of new compositions and dosage forms with effective delivery vehicles. The methods of informatics, bioinformatics, genomics and proteomics were extensively investigated for the development of new antimycotics. These techniques were employed in finding and identification of new molecular proteins in a fungal cell; in the determination of the selectivity of drug-protein interactions, evaluation of drug-drug interactions and synergism of drugs; determination of the structure-activity relationship (SAR) studies; determination of the molecular design of the most active, selective and safer drugs for the humans, animals and plants. In medical applications, the methods of information analysis and pharmacogenomics allows to take into account the individual phenotype of the patient, the level of expression of the targets of antifungal drugs when choosing antifungal agents and its dosage. This review article incorporates some of the most significant studies covering the basic structures and approaches for the synthesis of antifungal drugs and the directions for their further development.

scholarly journals Synergistic Effects of Amiodarone and Fluconazole on Candida tropicalis Resistant to Fluconazole

2013 ◽  
Vol 57 (4) ◽  
pp. 1691-1700 ◽  
Author(s):  
Cecília Rocha da Silva ◽  
João Batista de Andrade Neto ◽  
José Júlio Costa Sidrim ◽  
Maria Rozzelê Ferreira Ângelo ◽  
Hemerson Iury Ferreira Magalhães ◽  
...  
Keyword(s):  
Candida Tropicalis ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Synergistic Effects ◽  
Antifungal Drugs ◽  
Cross Resistance ◽  
Combination Drug ◽  
Content Type ◽  
Effective Strategies ◽  
Drug Of Choice

ABSTRACTThere have recently been significant increases in the prevalence of systemic invasive fungal infections. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapies have become one of the most widely used and effective strategies to alleviate this problem. Amiodarone (AMD) is classically used for the treatment of atrial fibrillation and is the drug of choice for patients with arrhythmia. Recent studies have shown broad antifungal activity of the drug when administered in combination with fluconazole (FLC). In the present study, we induced resistance to fluconazole in six strains ofCandida tropicalisand evaluated potential synergism between fluconazole and amiodarone. The evaluation of drug interaction was determined by calculating the fractional inhibitory concentration and by performing flow cytometry. We conclude that amiodarone, when administered in combination with fluconazole, exhibits activity against strains ofC. tropicalisthat are resistant to fluconazole, which most likely occurs via changes in the integrity of the yeast cell membrane and the generation of oxidative stress, mitochondrial dysfunction, and DNA damage that could lead to cell death by apoptosis.

8-Hydroxyquinoline 1,2,3-triazole derivatives with promising and selective antifungal activity

2020 ◽  
Author(s):  
Nailí Moreira da Silva ◽  
Caroline de Bem Gentz ◽  
Paula Reginatto ◽  
Thaís Helena Maciel Fernandes ◽  
Taís Fernanda Andrzejewski Kaminski ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Fungal Species ◽  
Candida Guilliermondii ◽  
Microsporum Canis ◽  
Fusarium Spp ◽  
Candida Spp ◽  
Fungal Cell ◽  
Triazole Derivatives ◽  
Design And Synthesis ◽  
Time Kill

Abstract Fungal infections that affect humans and plants have increased significantly in recent decades. However, these pathogens are still neglected when compared to other infectious agents. Due to the high prevalence of these infections, the need for new molecules with antifungal potential is recognized, as pathogenic species are developing resistance to the main drugs available. This work reports the design and synthesis of 1,2,3-triazole derivatives of 8-hydroxyquinoline, as well as the determination of their activities against a panel of fungal species: Candida spp., Trichosporon asahii, Magnusiomyces capitatus, Microsporum spp., Trichophyton spp. and Fusarium spp. The triazoles 5-(4-phenyl-1H-1,2,3-triazol-1-yl)quinolin-8-ol (12) and 5-(4-(cyclohex-1-en-1-yl)-1H-1,2,3-triazol-1-yl)quinolin-8-ol (16) were more promising, presenting minimum inhibitory concentration (MIC) values between 1–16 µg/ml for yeast and 2–4 µg/ml for dermatophytes. However, no relevant anti-Fusarium spp. activity was observed. In the time-kill assays with Microsporum canis, 12 and 16 presented time-dependent fungicide profile at 96 h and 120 h in all evaluated concentrations, respectively. For Candida guilliermondii, 12 was fungicidal at all concentrations at 6 h and 16 exhibited a predominantly fungistatic profile. Both 12 and 16 presented low leukocyte toxicity at 4 µg/ml and the cell viability was close to 100% after the treatment with 12 at all tested concentrations. The sorbitol assay combined with SEM suggest that damages on the fungal cell wall could be involved in the activity of these derivatives. Given the good results obtained with this series, scaffold 4-(cycloalkenyl or phenyl)-5-triazol-8-hydroxyquinoline appears to be a potential pharmacophore for exploration in the development of new antifungal agents.

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