Antifungal Drugs: Mechanism of Action and Resistance

Ahmed, Muhammad Zeeshan; Rao, T. Srinivasa; Saeed, Ali; Mutahir, Zeeshan; Hameed, Shahzeb; Inayat, Samrana; Shahzad, Haseeba; Ullah, Najeeb; Abaid-Ullah, Muhammad; Ibrahim, Muhammad; Munir, Shehla; Javed, Asghar; Khan, Jallat; Khalid, Muhammad Fasih; Ahmed, Sarfraz

doi:10.1007/978-3-030-76320-6_5

Cited by 9 publications

(6 citation statements)

References 44 publications

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“…Analogs of flucytosine, echinocandins, griseofulvin, allylamines, and iodides-other human and animal drugs used to treat fungal infections-are not used in crop production as fungicides. Although possible, and observed occasionally, resistance to polyene macrolides is unstable and non-transmissible [137].…”

Section: Other Fungicidesmentioning

confidence: 99%

Antimicrobial Use and Resistance in Plant Agriculture: A One Health Perspective

2022

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Bactericides, fungicides, and other pesticides play an important role in the management of plant diseases. However, their use can result in residues on plants and in the environment, with potentially detrimental consequences. The use of streptomycin, oxytetracycline, copper-based products, and some fungicides is correlated with increased resistance among plant pathogens to these agents. Likewise, the recent rise in the incidence of environmental triazole fungicide-resistant Aspergillus fumigatus, the cause of aspergillosis in humans, has caused concern, particularly in Europe. Through horizontal gene transfer, genes can be exchanged among a variety of bacteria in the plant production environment, including phytopathogens, soil bacteria, and zoonotic bacteria that are occasionally present in that environment and in the food chain. Through mechanisms of horizontal gene transfer, co-resistance, cross-resistance, and gene up-regulation, resistance to one compound may confer resistance and multi-drug resistance to other similar, or even very dissimilar, compounds. Given the global rise in antimicrobial-resistant (AMR) organisms, and their effects on plant, animal, and human health, the prudent use of pesticides is required to maintain their effectiveness for food security and sustainable production, and to minimize the emergence and transmission of AMR organisms from horticultural sources.

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Section: Other Fungicidesmentioning

confidence: 99%

Antimicrobial Use and Resistance in Plant Agriculture: A One Health Perspective

2022

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“…The resistance mechanism of Candida sp. to nystatin was assigned to a decreased binding affinity between nystatin and sterols [85].…”

Section: Synergistic Antifungal Efficiency Of the Biogenic Zno Nanopa...mentioning

confidence: 99%

Facile Green Synthesis of Zinc Oxide Nanoparticles with Potential Synergistic Activity with Common Antifungal Agents against Multidrug-Resistant Candidal Strains

et al. 2022

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The high incidence of fungal resistance to antifungal drugs represents a global concern, contributing to high levels of morbidity and mortality, especially among immunocompromised patients. Moreover, conventional antifungal medications have poor therapeutic outcomes, as well as possible toxicities resulting from long-term administration. Accordingly, the aim of the present study was to investigate the antifungal effectiveness of biogenic zinc oxide nanoparticles (ZnO NPs) against multidrug-resistant candidal strains. Biogenic ZnO NPs were characterized using physicochemical methods, such as UV-vis spectroscopy, transmission electron microscopy (TEM), energy-dispersive X ray (EDX) spectroscopy, FTIR (Fourier transform infrared) spectroscopy and X-ray powder diffraction (XRD) analysis. UV spectral analysis revealed the formation of two absorption peaks at 367 and 506 nm, which preliminarily indicated the successful synthesis of ZnO NPs, whereas TEM analysis showed that ZnO NPs exhibited an average particle size of 22.84 nm. The EDX spectrum confirmed the successful synthesis of ZnO nanoparticles free of impurities. The FTIR spectrum of the biosynthesized ZnO NPs showed different absorption peaks at 3427.99, 1707.86, 1621.50, 1424.16, 1325.22, 1224.67, 1178.22, 1067.69, 861.22, 752.97 and 574.11 cm−1, corresponding to various functional groups. The average zeta potential value of the ZnO NPs was −7.45 mV. XRD analysis revealed the presence of six diffraction peaks at 2θ = 31.94, 34.66, 36.42, 56.42, 69.54 and 76.94°. The biogenic ZnO NPs (100µg/disk) exhibited potent antifungal activity against C. albicans, C. glabrata and C. tropicalis strains, with suppressive zone diameters of 24.18 ± 0.32, 20.17 ± 0.56 and 26.35 ± 0.16 mm, respectively. The minimal inhibitory concentration (MIC) of ZnO NPs against C. tropicalis strain was found to be 10 μg/mL, whereas the minimal fungicidal concentration (MFC) was found to be 20 μg/mL. Moreover, ZnO NPs revealed a potential synergistic efficiency with fluconazole, nystatin and clotrimazole antifungal drugs against C. albicans strain, whereas terbinafine, nystatin and itraconazole antifungal drugs showed a potential synergism with ZnO NPs against C. glabrata as a multidrug-resistant strain. In conclusion, pomegranate peel extract mediated green synthesis of ZnO NPs with potential physicochemical features and antimicrobial activity. The biosynthesized ZnO NPs could be utilized for formulation of novel drug combinations to boost the antifungal efficiency of commonly used antifungal agents.

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“…Cellular acidification and the cessation of enzymatic activity are initiated by the entry of hydrogen ions and the efflux of potassium ions from the fungal cell. Additionally, the cells let out leaks of carbohydrates and amino acids which finally leads to the indication of fungal cell death [ 55 ]. On the contrary, the antifungal mechanism of ZnO-NPs against candidal cells occurs through the generation of ROS, which disrupts the fungal cell’s oxidative system and oxidizes essential cellular components such as protein, DNA and enzymes, and ultimately blocking the cellular enzymatic system and preventing cellular replication and inducing cell death [ 56 ].…”

Section: Resultsmentioning

confidence: 99%

Synergistic Anticandidal Activities of Greenly Synthesized ZnO Nanomaterials with Commercial Antifungal Agents against Candidal Infections

et al. 2023

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The high occurrence of mycological resistance to conventional antifungal agents results in significant illness and death rates among immunodeficient patients. In addition, the underprivileged therapeutic results of conventional antifungal agents, besides the potential toxicity resulting from long term therapy necessitate the fabrication of efficient antimicrobial combinations. Hence, the objective of the present investigation is to synthesize, characterize and investigate the anticandidal action of green zinc oxide nanoparticles (ZnO-NPs) formulated using Camellia sinensis leaf extract against three candidal pathogens. The eco-friendly synthesized ZnO-NPs were characterized utilizing different physicochemical methods and their anticandidal potency was tested utilizing a disk diffusion assay. In this setting, the size of the biofabricated ZnO-NPs was detected using transmission electron microscope (TEM) micrographs, recording an average particle size of 19.380 ± 2.14 nm. In addition, zeta potential analysis revealed that the ZnO-NPs surface charge was −4.72 mV. The biogenic ZnO-NPs reveal the highest anticandidal activity against the C. tropicalis strain, demonstrating relative suppressive zones measured at 35.16 ± 0.13 and 37.87 ± 0.24 mm in diameter for ZnO-NPs concentrations of 50 and 100 μg/disk, respectively. Excitingly, Candida glabrata showed a high susceptibility to the biofabricated ZnO nanomaterials at both ZnO-NPs’ concentrations (50 and 100 μg/disk) compared to the control. Moreover, the biosynthesized ZnO-NPs revealed potential synergistic effectiveness with nystatin and terbinafine antifungal agents against the concerned strains. The maximum synergistic efficiency was noticed against the C. glabrata strain, demonstrating relative synergistic percentages of 23.02 and 45.9%, respectively. The biogenic ZnO-NPs revealed no hemolytic activity against human erythrocytes revealing their biosafety and hemocompatibility. Finally, the high anticandidal effectiveness of biogenic ZnO-NPs against the concerned candidal pathogens, as well as potential synergistic patterns with conventional antifungal agents such as nystatin and terbinafine, emphasize the prospective application of these combinations for the fabrication of biocompatible and highly efficient antifungal agents.

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Antifungal Drugs: Mechanism of Action and Resistance

Cited by 9 publications

References 44 publications

Antimicrobial Use and Resistance in Plant Agriculture: A One Health Perspective

Antimicrobial Use and Resistance in Plant Agriculture: A One Health Perspective

Facile Green Synthesis of Zinc Oxide Nanoparticles with Potential Synergistic Activity with Common Antifungal Agents against Multidrug-Resistant Candidal Strains

Synergistic Anticandidal Activities of Greenly Synthesized ZnO Nanomaterials with Commercial Antifungal Agents against Candidal Infections

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