scholarly journals Envisaging Antifungal Potential of Histatin 5: A Physiological Salivary Peptide

2021 ◽  
Vol 7 (12) ◽  
pp. 1070
Author(s):  
Pratibha Sharma ◽  
Mehak Chaudhary ◽  
Garima Khanna ◽  
Praveen Rishi ◽  
Indu Pal Kaur
Keyword(s):  
Candida Albicans ◽  
Fungicidal Activity ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
High Morbidity ◽  
Histatin 5 ◽  
Salivary Peptide ◽  
Antifungal Potential ◽  
Low Incidence ◽  
Human Infections

Fungi are reported to cause a range of superficial to invasive human infections. These often result in high morbidity and at times mortality. Conventional antifungal agents though effective invariably exhibit drug interactions, treatment-related toxicity, and fail to elicit significant effect, thus indicating a need to look for suitable alternatives. Fungi thrive in humid, nutrient-enriched areas. Such an environment is well-supported by the oral cavity. Despite this, there is a relatively low incidence of severe oral and periodontal fungal infections, attributed to the presence of antimicrobial peptides hosted by saliva, viz. histatin 5 (Hstn 5). It displays fungicidal activity against a variety of fungi including Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and unicellular yeast-like Saccharomyces cerevisiae. Candida albicans alone accounts for about 70% of all global fungal infections including periodontal disease. This review intends to discuss the scope of Hstn 5 as a novel recourse for the control of fungal infections.

scholarly journals The In Vitro Potential of 1-(1H-indol-3-yl) Derivatives against Candida spp. and Aspergillus niger as Tyrosinase Inhibitors

2021 ◽  
Vol 9 (10) ◽  
pp. 2070
Author(s):  
Teresa Gervasi ◽  
Giovanna Ginestra ◽  
Francesca Mancuso ◽  
Davide Barreca ◽  
Laura De Luca ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Niger ◽  
Fungicidal Activity ◽  
Candida Parapsilosis ◽  
Fungal Infections ◽  
Clinical Isolates ◽  
Candida Spp ◽  
Antifungal Potential ◽  
Tyrosinase Inhibitors

Given the increased antimicrobial resistance, global effort is currently focused on the identification of novel compounds, both of natural and chemical origin. The present study reports on the antifungal potential of 1-(1H-indol-3-yl) derivatives, previously known as tyrosinase inhibitors. The effect of seven compounds (indicated as 3a–g) was determined against Candida albicans ATCC 10531, three clinical isolates of Candida albicans, two clinical isolates of Candida glabrata, two clinical isolates of Candida parapsilosis and Aspergillus niger ATCC 16404. The effect of these derivatives on tyrosinase enzymatic activity was also evaluated. Results showed a fungicidal activity of compounds 3b, 3c and 3e against all tested strains at concentrations ranging between 0.250 and 1 mg/mL. Furthermore, the association between 3c and fluconazole and between 3b and caspofungin showed a trend of indifference tending toward synergism. Compound 3c was also able to inhibit microbial tyrosinase up to ~28% at the concentration of 0.250 mg/mL. These data could help provide novel therapeutics for topical use to treat fungal infections and increase the potential effectiveness of the association between novel compounds and commercial antifungals in order to combat drug resistance.

scholarly journals ANTI-CANDIDA ALBICANS ACTIVITY OF THE ASSOCIATION OF CITRONELAL WITH ANFOTERICIN B OR WITH CETOCONAZOLE

2019 ◽  
Vol 16 (31) ◽  
pp. 250-257
Author(s):  
Patrícia Duarte Costa SILVA ◽  
Brenda Lavínia Calixto dos SANTOS ◽  
Gustavo Lima SOARES ◽  
Wylly Araújo de OLIVEIRA
Keyword(s):  
Candida Albicans ◽  
Antifungal Activity ◽  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Mortality Rates ◽  
New Drugs ◽  
High Morbidity ◽  
Isolated Species

Fungal infections caused by species of the genus Candida are responsible for high morbidity and mortality rates, mainly affecting immunocompromised individuals. Among fungi, Candida albicans is the most frequently isolated species of clinical specimens. A problem associated with increased resistance of pathogenic fungi to the agents used in the therapeutic regimen and the limited number of drugs to cure these infections. As a result, the search for new drugs with antifungal activity has become increasingly important. The aim of this study is to study the antifungal activity of citronellal alone and in combination with amphotericin B or ketoconazole. The Minimal Inhibitory Concentration of citronellal, amphotericin B and ketoconazole against strains of Candida albicans were evaluated by the microdilution technique, and the Minimum Fungicide Concentration of citronellal against the same strains was also performed. Through the checkerboard methodology the effect of the combination of citronelal with amphotericin B or with ketoconazole was determined. This study showed that the association of citronellal with ketoconazole was shown to be an additive against one of the strains of C. albicans and indifferent to another strain. While the combined activity of citronellal and amphotericin B demonstrated an indifferent effect on the strains tested.

scholarly journals Candida albicans Sterol C-14 Reductase, Encoded by the ERG24 Gene, as a Potential Antifungal Target Site

2002 ◽  
Vol 46 (4) ◽  
pp. 947-957 ◽  
Author(s):  
N. Jia ◽  
B. Arthington-Skaggs ◽  
W. Lee ◽  
C. A. Pierson ◽  
N. D. Lees ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Brefeldin A ◽  
Agricultural Applications ◽  
Mouse Model System ◽  
Cellular Inhibitors ◽  
Germ Tubes ◽  
Doubling Times

ABSTRACT The incidence of fungal infections has increased dramatically, which has necessitated additional and prolonged use of the available antifungal agents. Increased resistance to the commonly used antifungal agents, primarily the azoles, has been reported, thus necessitating the discovery and development of compounds that would be effective against the major human fungal pathogens. The sterol biosynthetic pathway has proved to be a fertile area for antifungal development, and steps which might provide good targets for novel antifungal development remain. The sterol C-14 reductase, encoded by the ERG24 gene, could be an effective target for drug development since the morpholine antifungals, inhibitors of Erg24p, have been successful in agricultural applications. The ERG24 gene of Candida albicans has been isolated by complementation of a Saccharomyces cerevisiae erg24 mutant. Both copies of the C. albicans ERG24 gene have been disrupted by using short homologous regions of the ERG24 gene flanking a selectable marker. Unlike S. cerevisiae, the C. albicans ERG24 gene was not required for growth, but erg24 mutants showed several altered phenotypes. They were demonstrated to be slowly growing, with doubling times at least twice that of the wild type. They were also shown to be significantly more sensitive to an allylamine antifungal and to selected cellular inhibitors including cycloheximide, cerulenin, fluphenazine, and brefeldin A. The erg24 mutants were also slightly resistant to the azoles. Most importantly, erg24 mutants were shown to be significantly less pathogenic in a mouse model system and failed to produce germ tubes upon incubation in human serum. On the basis of these characteristics, inhibitors of Erg24p would be effective against C. albicans.

Raynaud's Phenomenon of the Nipples: An Elusive Diagnosis

2007 ◽  
Vol 23 (2) ◽  
pp. 191-193 ◽  
Author(s):  
Carolyn Morino ◽  
Susan M. Winn
Keyword(s):  
Candida Albicans ◽  
Case Report ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Raynaud’S Phenomenon ◽  
Raynaud's Phenomenon

Pain and throbbing of the nipples associated with Raynaud's phenomenon often mimics yeast or fungal infections. Breastfeeding mothers with Raynaud's of the nipples are often treated inappropriately for organisms such as Candida Albicans with topical or systemic antifungal agents. This case report describes the eventual diagnosis of Raynaud's phenomenon of the nipples in a breastfeeding mother who was initially treated for yeast. J Hum Lact. 23(2):191-193.

scholarly journals Studies on the combinations of some herbals with various chemical entities as a potent antifungal agents

2021 ◽  
Vol 9 (2) ◽  
pp. 103-111
Author(s):  
Nitin S Kolhe ◽  
V H Bhaskar ◽  
Shubham Ghosh ◽  
Sanskruti Kharavtekar ◽  
Savni Prabhu ◽  
...  
Keyword(s):  
Public Health ◽  
Adverse Effects ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
High Morbidity ◽  
Herbal Extracts ◽  
Medication Treatment ◽  
Lead Compounds ◽  
Significant Burden ◽  
Gold Standards

A widespread increase in the prevalence of fungal infections has been documented in recent decades. Candida albicans infections, which are frequently refractory and linked with high morbidity and mortality, place a significant burden on public health, despite the fact that existing antifungal medicines are restricted and associated with toxicity. Fungi are one of the most underappreciated killers, as evidenced by the fact that Amphotericin B and other commercially available antifungal therapies are still recognized as gold standards. The majority of commonly used antifungal medications have toxicity, effectiveness, and cost disadvantages. As a result of these limitations, there is a growing demand for the development of a novel antifungal medication treatment that acts selectively on new targets while having the fewest adverse effects. Natural goods, whether as pure phytocompounds or regulated plant extracts, give prospects for the development of lead compounds that may subsequently be turned into diverse synthetic medications with the appropriate alterations. These herbs can also be used as a component of a herbal synthetic combination, lowering the minimum required dose of the synthetic medicine (when taken singly) and reducing the risk of adverse effects. The goal of this research is to reduce the minimum required concentrations of today's antifungal medications by mixing them with a few less well-known herbal extracts while maintaining their efficacy.

scholarly journals Multifactorial Mechanisms of Tolerance to Ketoconazole in Candida albicans

2021 ◽  
Author(s):  
Yi Xu ◽  
Hui Lu ◽  
Shuo Zhu ◽  
Wan-Qian Li ◽  
Yuan-ying Jiang ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Medical Procedures ◽  
Drug Classes ◽  
Immunocompromised Status ◽  
Invasive Medical Procedures ◽  
Global Threat

Due to the ever-expanding range of invasive medical procedures and treatments, invasive fungal infections now pose a serious global threat to many people living in an immunocompromised status. Like humans, fungi are eukaryotic, which significantly limits the number of unique antifungal targets; the current arsenal of antifungal agents is limited to just three frontline drug classes.

Prolonged voriconazole treatment in a patient with chronic lymphocytic leukemia resulting in a litany of chronic overlapping toxicities

2018 ◽  
Vol 25 (3) ◽  
pp. 747-753 ◽  
Author(s):  
Caitlin R Rausch ◽  
Dimitrios P Kontoyiannis
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Lymphocytic Leukemia ◽  
Suppressive Therapy ◽  
Prolonged Treatment ◽  
High Morbidity ◽  
Limited Experience ◽  
Continuous Use ◽  
Visual Disturbances

Voriconazole is a triazole antifungal with activity against a number of yeast and mold species including Candida, Aspergillosis, Fusarium, and Coccidioides. Invasive fungal infections are associated with high morbidity and mortality, prolonged treatment courses, and occasionally lifelong suppressive therapy. Voriconazole therapy can result in a number of acute toxicities that clinicians are frequently aware of including hepatotoxicity, visual disturbances, and hallucinations; however, there is limited experience with extended durations of voriconazole therapy. We describe the case of a 62-year-old man who developed Coccidioides meningitis as a result of prolonged neutropenia from treatment for chronic lymphocytic leukemia. He was initially treated with a number of different antifungal agents including voriconazole, liposomal amphotericin B, fluconazole, and itraconazole; however, he developed acute toxicity due to those agents. He was successfully re-challenged with voriconazole, and maintained therapeutic serum concentrations throughout treatment. As a result of prolonged voriconazole exposure of over 14 years, he has suffered a number of toxicities, most significantly including actinic keratosis, squamous cell carcinoma, and skeletal fluorosis. To our knowledge, this is the longest continuous use of voriconazole therapy currently in the literature.

Recent Advances in Azole Based Scaffolds as Anticandidal Agents

2019 ◽  
Vol 16 (5) ◽  
pp. 492-501 ◽  
Author(s):  
Prabhuodeyara Math Gurubasavaraj ◽  
Jasmith Shivayya Charantimath
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Candida Albicans ◽  
Drug Interactions ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Fungal Virulence ◽  
Compromised Patients

Aim:The present review aims to explore the development of novel antifungal agents, such as pharmacology, pharmacokinetics, spectrum of activity, safety, toxicity and other aspects that involve drug-drug interactions of the azole antifungal agents.Introduction:Fungal infections in critically ill and immune-compromised patients are increasing at alarming rates, caused mainly by Candida albicans an opportunistic fungus. Despite antifungal annihilators like amphotericin B, azoles and caspofungin, these infections are enormously increasing. The unconventional increase in such patients is a challenging task for the management of antifungal infections especially Candidiasis. Moreover, problem of toxicity associated with antifungal drugs on hosts and rise of drug-resistance in primary and opportunistic fungal pathogens has obstructed the success of antifungal therapy.Conclusion:Hence, to conflict these problems new antifungal agents with advanced efficacy, new formulations of drug delivery and novel compounds which can interact with fungal virulence are developed and used to treat antifungal infections.

Candida, the Opportunistic Human Pathogen

2020 ◽  
Vol 981 ◽  
pp. 309-315
Author(s):  
Sakina Shahabudin ◽  
Nina Suhaity Azmi
Keyword(s):  
Candida Albicans ◽  
Environmental Conditions ◽  
Antifungal Agents ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
High Morbidity ◽  
Human Pathogen ◽  
Human Pathogens ◽  
Normal Human ◽  
Opportunistic Human Pathogen

Candida species are known human pathogens that have caused high morbidity and mortality among affected individuals. Candida albicans can switch forms from yeast to hyphae, in which both forms are virulent. Due to its commensal status in normal human microflora, C. albicans poses a virtual threat to humankind because of their dimorphism ability under opportunistic environmental conditions. Because of the increased usage of prophylactic antifungal agents in the treatment of candidiasis, reports of Candida species developing antifungal resistance are increasing. Recent observations of cross-reaction between different classes of antifungal drugs that could yield multidrug-resistant pathogenic Candida species are concerns that need to be urgently addressed.

scholarly journals Sequencing, Disruption, and Characterization of the Candida albicans Sterol Methyltransferase (ERG6) Gene: Drug Susceptibility Studies in erg6 Mutants

1998 ◽  
Vol 42 (5) ◽  
pp. 1160-1167 ◽  
Author(s):  
K. L. Jensen-Pergakes ◽  
M. A. Kennedy ◽  
N. D. Lees ◽  
R. Barbuch ◽  
C. Koegel ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Antifungal Agents ◽  
Genomic Library ◽  
Fungal Infections ◽  
Brefeldin A ◽  
Drug Susceptibility ◽  
Metabolic Inhibitors ◽  
Sterol Synthesis ◽  
Methyltransferase Gene ◽  
Sterol Methyltransferase

ABSTRACT The rise in the frequency of fungal infections and the increased resistance noted to the widely employed azole antifungals make the development of new antifungals imperative for human health. The sterol biosynthetic pathway has been exploited for the development of several antifungal agents (allylamines, morpholines, azoles), but additional potential sites for antifungal agent development are yet to be fully investigated. The sterol methyltransferase gene (ERG6) catalyzes a biosynthetic step not found in humans and has been shown to result in several compromised phenotypes, most notably markedly increased permeability, when disrupted in Saccharomyces cerevisiae. The Candida albicans ERG6 gene was isolated by complementation of a S. cerevisiae erg6 mutant by using a C. albicans genomic library. Sequencing of theCandida ERG6 gene revealed high homology with theSaccharomyces version of ERG6. The first copy of the Candida ERG6 gene was disrupted by transforming with the URA3 blaster system, and the second copy was disrupted by both URA3 blaster transformation and mitotic recombination. The resulting erg6 strains were shown to be hypersusceptible to a number of sterol synthesis and metabolic inhibitors, including terbinafine, tridemorph, fenpropiomorph, fluphenazine, cycloheximide, cerulenin, and brefeldin A. No increase in susceptibility to azoles was noted. Inhibitors of the ERG6gene product would make the cell increasingly susceptible to antifungal agents as well as to new agents which normally would be excluded and would allow for clinical treatment at lower dosages. In addition, the availability of ERG6 would allow for its use as a screen for new antifungals targeted specifically to the sterol methyltransferase.

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