Natamycin is a polyene macrolide antibiotics with strong and broad spectrum antifungal activity. It not only effectively inhibits the growth and reproduction of fungi, but also prevents the formation of some mycotoxins. Consequently, it has been approved for use as an antifungal food preservative in most countries, and is also widely used in agriculture and healthcare. Streptomyces natalensis and Streptomyces chatanoogensis are the main producers of natamycin. This review summarizes the biosynthesis and regulatory mechanism of natamycin, as well as the strategies for improving natamycin production. Moreover, the future perspectives on natamycin research are discussed.
Antifungal Agents/pharmacology* ; Fungi ; Natamycin ; Streptomyces

The advancement of phytochemical and phytopharmacological sciences has enabled elucidation of the composition and biological activities of several medicinal plant products including plant extract and essential oils. These products have been widely used around the world since ancient times for the treatment of various disorders such as diabetes, hypertension, peptic ulcer disease, microbial infection, sexual disorder and many more. Its popularity in the modern system of medicine is mainly due to their availability and fewer adverse reactions compared to synthetic drugs. Various scientifific investigations have been conducted to look for the potential of the extract from the plant or isolated compounds for the continued use of these products in the treatment and prevention of various kinds of human diseases. It is evident from the available literature and scientifific investigations that many plant species possess potential for use as a benefificial therapeutic remedy with multiple pharmacological actions such as analgesic, anti-inflflammatory, antipyretic, hypoglycemic, hypotensive, antimicrobial, antiulcer and anticonvulsant activities. The present review aims to provide relevant updated information about certain plant products, its composition, preparation and its fungicidal or fungistatic effects on different species of fungus as evaluated by studies done in the past. It introduces six medicinal plants that have been studied for their antifungal property and are found to be effective. The overall objective is to provide comprehensive information about the use of plant extract and essential oil for treating fungal infections and to explore the evidence supporting its effectiveness in treating fungal diseases without causing any serious adverse reactions.
Antifungal Agents ; pharmacology ; Plant Extracts ; pharmacology ; Plant Oils ; pharmacology

Steroidal saponins have a wide range of pharmacological effects and biological activities, such as anti-tumor, antifungal, hypoglycemic, immune regulation, insecticides, etc. In the last ten years, some new structures of steroidal saponins compounds were found from natural plants, they have some new and different activities. In order to accelerate the research on the drug innovation of steroidal saponins, we summarized the new progress of the research on such compounds.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Antifungal Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Humans ; Hypoglycemic Agents ; pharmacology ; Saponins ; pharmacology ; Steroids ; pharmacology

Tetrahydroisoquinoline alkaloids distributed widely in the nature and some have a broad application in clinic. More attention has been paid in recent years on this type of alkaloid, owing to the diverse range of biological activities exhibited by these alkaloids and the discovery of new functional mechanisms and molecular targets underlying these activities. This article summarized the recent advances in the biological activities and functional mechanism of tetrahydroisoquinoline, which included the activities such as antitumor, antibiotic, antivirus, anti-inflammatory, anticoagulation, bronchodilation, and the action on central nervous system, with the purpose of providing some ideas in the study of biological activity of this type of alkaloid and in the search for lead-compound and rational drug design.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Anticonvulsants ; pharmacology ; Antifungal Agents ; pharmacology ; Antineoplastic Agents ; pharmacology ; Antiviral Agents ; pharmacology ; Bronchodilator Agents ; pharmacology ; Central Nervous System Agents ; pharmacology ; Fibrinolytic Agents ; pharmacology ; Humans ; Neuroprotective Agents ; pharmacology ; Tetrahydroisoquinolines ; chemical synthesis ; chemistry ; pharmacology

Previously, we reported that epigallocatechin 3-O-gallate (EGCg) has growth-inhibitory effect on clinical isolates of Candida species. In this study, we investigated the antifungal activity of EGCg and antifungal agents against thirty-five of dermatophytes clinically isolated by the international guidelines (M38-A2). All isolates exhibited good susceptibility to EGCg (MIC50, 2-4 microg/mL, MIC90, 4-8 microg/mL, and geometric mean (GM) MICs, 3.36-4 microg/mL) than those of fluconazole (MIC50, 2-16 microg/mL, MIC90, 4-32 microg/mL, and GM MICs, 3.45-25.8 microg/mL) and flucytosin (MIC50, MIC90, and GM MICs, >64 microg/mL), although they were less susceptible to other antifungal agents, such as amphotericin B, itraconazole, and miconazole. These activities of EGCg were approximately 4-fold higher than those of fluconazole, and were 4 to 16-fold higher than flucytosin. This result indicates that EGCg can inhibit pathogenic dermatophyte species. Therefore, we suggest that EGCg may be effectively used solely as a possible agent or combined with other antifungal agents for antifungal therapy in dermatophytosis.
Antifungal Agents/*pharmacology ; Arthrodermataceae/*drug effects/isolation & purification ; Catechin/*analogs & derivatives/pharmacology ; Microbial Sensitivity Tests

OBJECTIVETo performance susceptibility testing of antifungal agents. Due to the increasing number of resistant strains, susceptibility testing of antifungal agents is gaining importance.

METHODSWe compared the results of standard macrotube dilution reference method with two different microdilution methods, as well as the disc diffusion method in order to test the susceptibility of 150 Candida strains to fluconazole.

RESULTSOverall correlation between microdilution and macrodilution methods was 86%. It was 91% between the Minimal Inhibitory Concentrations obtained from macrodilution and disc diffusion zone diameters.

CONCLUSIONThe disc diffusion test was evaluated as a low-cost, reproducible, and efficient way of assessing the in vitro susceptibility of Candida strains to fluconazole.

The incidence of systemic fungal infections have increased dramatically, moreover, drug resistance including either primary (intrinsic) or secondary (acquired) resistance, becomes one of the main reasons accounting for the failure of treating invasive fungal infections in the past decades. Nowadays, clinically available antifungal drugs are limited and their combination in antifungal therapy was not effective. It is expected to be a new strategy to synergistically sensitize antifungal drugs against drug-resistant fungi by using new small molecules. Based on the study in our research group and the reported work of others, we reviewed the research of the natural products which have synergistic effect with the antifungal agents against drug-resistant fungi. This review focused on the resource, structure, pharmacological activity, and action mechanism of the compounds, as well as somewhat in common, and would provide theoretical base for seeking new drug against drug-resistance fungi.
Antifungal Agents ; chemistry ; pharmacology ; Biological Products ; chemistry ; pharmacology ; Drug Synergism ; Fungi ; drug effects

The aim of this paper was to investigate the effect of berberine hydrochloride on the cell wall integrity of Candida albicans hypha. The minimal inhibitory concentration(MIC) of berberine hydrochloride against clinical and standard C. albicans strains was detected by micro liquid-based dilution method; the effect of berberine hydrochloride on the colony formation of C. albicans SC5314 was investigated by spot assay; the effect of berberine hydrochloride on the metabolism of C. albicans SC5314 hypha was checked by XTT reduction assay, and the viability of C. albicans SC5314 hypha was tested by fluorescent staining assay. The effect of berberine hydrochloride on the morphology of C. albicans SC5314 hypha was examined by scanning electron microscope. The changes in the cell wall of C. albicans SC5314 hypha after berberine hydrochloride treatment were detected by transmission electron microscopy. The effect of berberine hydrochloride on β-glucan from C. albicans SC5314 was detected by flow cytometry. The effect of berberine hydrochloride on hypha-specific gene ECE1 and β-glucan synthase genes FKS1 and FKS2 in C. albicans was examined by qRT-PCR. The results showed that berberine hydrochloride showed a strong inhibitory effect on both clinical and standard strains of C. albicans, and the MIC was 64-128 μg·mL~(-1). Spot assay, XTT redunction assay and fluorescent staining assay showed that with the increase of berberine hydrochloride concentration, the viability of C. albicans SC5314 gradually decreased. The transmission electron microscopy scanning assay showed that this compound could cause cell wall damage of C. albicans. The flow cytometry analysis showed the exposure degree of C. albicans β-glucan. The qRT-PCR further showed that berberine hydrochloride could significantly down-regulate hypha-specific gene ECE1 and β-glucan synthase-related gene FKS1 and FKS2. In conclusion, this compound can down-regulate C. albicans and β-glucan synthase-related gene expressions, so as to destroy the cell wall structure of C. albicans, expose β-glucan and damage the integrity of the wall.
Antifungal Agents/pharmacology* ; Berberine/pharmacology* ; Candida albicans/genetics* ; Cell Wall ; Hyphae ; Microbial Sensitivity Tests

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.
Animals ; Mice ; Candida albicans ; Candidiasis, Oral/drug therapy* ; Antifungal Agents/pharmacology* ; Hyphae ; Artemisinins/pharmacology*

Candida albicans is one of the major causes of invasive fungal infections and a serious opportunistic pathogen in immunocompromised individuals. The antimicrobial peptide AMP-17 has prominent anti-Candida activity, and proteomic analysis revealed significant differences in the expression of cell wall (XOG1) and oxidative stress (SRR1) genes upon the action of AMP-17 on C. albicans, suggesting that AMP-17 may exert anti-C. albicans effects by affecting the expression of XOG1 and SRR1 genes. To further investigate whether XOG1 and SRR1 genes were the targets of AMP-17, C. albicans xog1Δ/Δ and srr1Δ/Δ mutants were constructed using the clustered regulatory interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system. Phenotypic observations revealed that deletion of two genes had no significant effect on C. albicans growth and biofilm formation, whereas XOG1 gene deletion affected in vitro stress response and mycelium formation of C. albicans. Drug sensitivity assay showed that the MIC₈₀ values of AMP-17 against xog1Δ/Δ and srr1Δ/Δ mutants increased from 8 μg/mL (for the wild type C. albicans SC5314) to 16 μg/mL, while the MIC₈₀ values against srr1Δ/Δ: : srr1 revertants decreased to the level of the wild type SC5314. In addition, the ability of AMP-17 to inhibit biofilm formation of both deletion strains was significantly reduced compared to that of wild type SC5314, indicating that the susceptibility of the deletion mutants to AMP-17 was reduced in both the yeast state and during biofilm formation. These results suggest that XOG1 and SRR1 genes are likely two of the potential targets for AMP-17 to exert anti-C. albicans effects, which may facilitate further exploration of the antibacterial mechanism of novel peptide antifungal drugs.
Humans ; Candida albicans ; Antimicrobial Peptides ; Proteomics ; Peptides/pharmacology* ; Transcription Factors/metabolism* ; Antifungal Agents/pharmacology*