Antifungal agents commonly used in the superficial and mucosal candidiasis treatment: mode of action and resistance development

Bondaryk, Małgorzata; Kurzątkowski, W; Staniszewska, Monika

doi:10.5114/pdia.2013.38358

Cited by 100 publications

(80 citation statements)

References 80 publications

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“…In C. glabrata and C. albicans , mutation in cytosine deaminase confers primary resistance to 5-FC, and deficiencies in cytosine permease activity have also been associated with resistance in Candida species (Hope et al, 2004; Vandeputte et al, 2011). Cytosine permease is involved in the uptake of 5-FC, after which cytosine deaminase produces 5-fluorouracil using cytosine; thus, 5-FC resistance is associated with deficiency in enzymes related to uptake, transport and transformation of 5-FC that result in failure to metabolize to the active drug (Bondaryk et al, 2013). A C. lusitaniae mutant lacking the enzyme uracil phosphoribosyl transferase, encoded by the gene FUR1 (Papon et al, 2007), exhibits secondary resistance to 5-FC.…”

Section: Molecular Mechanisms Of Antifungal Resistancementioning

confidence: 99%

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

et al. 2017

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The high rates of morbidity and mortality caused by fungal infections are associated with the current limited antifungal arsenal and the high toxicity of the compounds. Additionally, identifying novel drug targets is challenging because there are many similarities between fungal and human cells. The most common antifungal targets include fungal RNA synthesis and cell wall and membrane components, though new antifungal targets are being investigated. Nonetheless, fungi have developed resistance mechanisms, such as overexpression of eﬄux pump proteins and biofilm formation, emphasizing the importance of understanding these mechanisms. To address these problems, different approaches to preventing and treating fungal diseases are described in this review, with a focus on the resistance mechanisms of fungi, with the goal of developing efficient strategies to overcoming and preventing resistance as well as new advances in antifungal therapy. Due to the limited antifungal arsenal, researchers have sought to improve treatment via different approaches, and the synergistic effect obtained by the combination of antifungals contributes to reducing toxicity and could be an alternative for treatment. Another important issue is the development of new formulations for antifungal agents, and interest in nanoparticles as new types of carriers of antifungal drugs has increased. In addition, modifications to the chemical structures of traditional antifungals have improved their activity and pharmacokinetic parameters. Moreover, a different approach to preventing and treating fungal diseases is immunotherapy, which involves different mechanisms, such as vaccines, activation of the immune response and inducing the production of host antimicrobial molecules. Finally, the use of a mini-host has been encouraging for in vivo testing because these animal models demonstrate a good correlation with the mammalian model; they also increase the speediness of as well as facilitate the preliminary testing of new antifungal agents. In general, many years are required from discovery of a new antifungal to clinical use. However, the development of new antifungal strategies will reduce the therapeutic time and/or increase the quality of life of patients.

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Section: Molecular Mechanisms Of Antifungal Resistancementioning

confidence: 99%

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

et al. 2017

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“…Hitherto, there are several major antifungal drugs targeting C. albicans as follows: pyrimidines like 5-fluorocytosine, polyenes including amphotericin B and nystatin, azoles such as fluconazole, and echinocandins such as caspofungin. Due to drug resistance encountered during treatments with all four types of drugs and the reported side effects, a search for more potential antifungal agents is warranted (Bondaryk et al 2013; Geronikaki et al 2013; Hamill 2013; Silva et al 2014). Lung infections caused by non- Aspergillus molds are increasing in specific populations, and new problems of susceptibility and resistance have emerged (Paiva and Pereira 2013).…”

Section: Introductionmentioning

confidence: 99%

Antifungal and antiviral products of marine organisms

Cheung

Wong

Pan

et al. 2014

Appl Microbiol Biotechnol

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Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (−)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (−)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1–5 (TH 1–5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper β-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the afore-mentioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The prospects of employing them in clinical practice are promising in view of the wealth of these compounds from marine organisms. The compounds may also be used in agriculture and the food industry.

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“…The echinocandins inhibit the synthesis of the essential cell wall polymer ␤-(1,3)-glucan (8). However, antifungal resistance is limiting the effectiveness of both azoles and echinocandins (9)(10)(11), and toxicity from treatment with amphotericin B can be a serious problem for patients (12). The development of new antifungal drugs is urgently needed (13)(14)(15).…”

mentioning

confidence: 99%

β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity

et al. 2017

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Candida albicans is among the most common human fungal pathogens, causing a broad range of infections, including life-threatening systemic infections. The cell wall of C. albicans is the interface between the fungus and the innate immune system. The cell wall is composed of an outer layer enriched in mannosylated glycoproteins (mannan) and an inner layer enriched in ␤-(1,3)-glucan and chitin. Detection of C. albicans by Dectin-1, a C-type signaling lectin specific for ␤-(1,3)-glucan, is important for the innate immune system to recognize systemic fungal infections. Increased exposure of ␤-(1,3)-glucan to the immune system occurs when the mannan layer is altered or removed in a process called unmasking. Nanoscale changes to the cell wall during unmasking were explored in live cells with atomic force microscopy (AFM). Two mutants, the cho1Δ/Δ and kre5Δ/Δ mutants, were selected as representatives that exhibit modest and strong unmasking, respectively. Comparisons of the cho1Δ/Δ and kre5Δ/Δ mutants to the wild type reveal morphological changes in their cell walls that correlate with decreases in cell wall elasticity. In addition, AFM tips functionalized with Dectin-1 revealed that the forces of binding of Dectin-1 to all of the strains were similar, but the frequency of binding was highest for the kre5Δ/Δ mutant, decreased for the cho1Δ/Δ mutant, and rare for the wild type. These data show that nanoscale changes in surface topology are correlated with increased Dectin-1 adhesion and decreased cell wall elasticity. AFM, using tips functionalized with immunologically relevant molecules, can map epitopes of the cell wall and increase our understanding of pathogen recognition by the immune system.

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Antifungal agents commonly used in the superficial and mucosal candidiasis treatment: mode of action and resistance development

Cited by 100 publications

References 80 publications

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

Antifungal and antiviral products of marine organisms

β-(1,3)-Glucan Unmasking in Some Candida albicans Mutants Correlates with Increases in Cell Wall Surface Roughness and Decreases in Cell Wall Elasticity

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