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Mode of action and synergistic effect of valinomycin and cereulide with amphotericin B against Candida albicans and Cryptococcus albidus.
J Mycol Med. 2018 Mar; 28(1):112-121.JM

Abstract

Both valinomycin and cereulide are cyclic depsipeptides and are known K[+] ion-selective ionophores. Valinomycin and cereulide feature low minimum inhibitory concentration (MIC) values against Candida albicans and Cryptococcus albidus. This study aims at investigating the mode of action and verifying the efficacy of valinomycin or cereulide alone and in combination with amphotericin B (AmB) in vitro against both microorganisms. Based on the results from membrane permeability and fluidity assays for detection of plasma membrane permeabilization and membrane dynamics, the present study demonstrated that valinomycin and cereulide exhibit antifungal activity against C. albicans and C. albidus by interrupting membrane-associated function. The mode of action of both valinomycin and cereulide are similar with that of AmB. Time-kill kinetics assay showed that valinomycin and cereulide exhibit fungistatic activity, whereas AmB features fungicidal activity. Additionally, the combination of compounds between each cyclic peptide and AmB reached maximal fungicidal activity more rapidly than AmB alone. This result corresponded with findings of scanning electron microscopy, fractional inhibitory concentration index and minimum fungicidal concentration (MFC)/MIC ratio, indicating that combinations of the drugs show synergistic effects for inhibiting the growth of these fungal strains. Sorbitol and ergosterol assays showed that both cyclic peptides affected cell wall and membrane components due to increases in MIC value, as observed in medium with sorbitol and ergosterol. Valinomycin and cereulide may promote permeability of fungal cell wall and cell membrane when used in combination with AmB.

Authors+Show Affiliations

Department of Chemistry, Laboratory of Organic Synthesis, Chulabhorn Research Institute, 54, Vipavadee-Rangsit Highway, Bangkok 10210, Thailand.Department of Chemistry, Laboratory of Organic Synthesis, Chulabhorn Research Institute, 54, Vipavadee-Rangsit Highway, Bangkok 10210, Thailand.Department of Chemistry, Laboratory of Organic Synthesis, Chulabhorn Research Institute, 54, Vipavadee-Rangsit Highway, Bangkok 10210, Thailand.Department of Chemistry, Laboratory of Organic Synthesis, Chulabhorn Research Institute, 54, Vipavadee-Rangsit Highway, Bangkok 10210, Thailand.Department of Chemistry, Laboratory of Organic Synthesis, Chulabhorn Research Institute, 54, Vipavadee-Rangsit Highway, Bangkok 10210, Thailand.Department of Chemistry, Laboratory of Organic Synthesis, Chulabhorn Research Institute, 54, Vipavadee-Rangsit Highway, Bangkok 10210, Thailand. Electronic address: supanna@cri.or.th.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29276078

Citation

Makarasen, A, et al. "Mode of Action and Synergistic Effect of Valinomycin and Cereulide With Amphotericin B Against Candida Albicans and Cryptococcus Albidus." Journal De Mycologie Medicale, vol. 28, no. 1, 2018, pp. 112-121.
Makarasen A, Reukngam N, Khlaychan P, et al. Mode of action and synergistic effect of valinomycin and cereulide with amphotericin B against Candida albicans and Cryptococcus albidus. J Mycol Med. 2018;28(1):112-121.
Makarasen, A., Reukngam, N., Khlaychan, P., Chuysinuan, P., Isobe, M., & Techasakul, S. (2018). Mode of action and synergistic effect of valinomycin and cereulide with amphotericin B against Candida albicans and Cryptococcus albidus. Journal De Mycologie Medicale, 28(1), 112-121. https://doi.org/10.1016/j.mycmed.2017.11.007
Makarasen A, et al. Mode of Action and Synergistic Effect of Valinomycin and Cereulide With Amphotericin B Against Candida Albicans and Cryptococcus Albidus. J Mycol Med. 2018;28(1):112-121. PubMed PMID: 29276078.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mode of action and synergistic effect of valinomycin and cereulide with amphotericin B against Candida albicans and Cryptococcus albidus. AU - Makarasen,A, AU - Reukngam,N, AU - Khlaychan,P, AU - Chuysinuan,P, AU - Isobe,M, AU - Techasakul,S, Y1 - 2017/12/21/ PY - 2017/04/22/received PY - 2017/11/22/revised PY - 2017/11/29/accepted PY - 2017/12/26/pubmed PY - 2019/1/31/medline PY - 2017/12/26/entrez KW - Amphotericin B KW - Antifungal activity KW - Cereulide KW - Synergistic effect KW - Valinomycin SP - 112 EP - 121 JF - Journal de mycologie medicale JO - J Mycol Med VL - 28 IS - 1 N2 - Both valinomycin and cereulide are cyclic depsipeptides and are known K[+] ion-selective ionophores. Valinomycin and cereulide feature low minimum inhibitory concentration (MIC) values against Candida albicans and Cryptococcus albidus. This study aims at investigating the mode of action and verifying the efficacy of valinomycin or cereulide alone and in combination with amphotericin B (AmB) in vitro against both microorganisms. Based on the results from membrane permeability and fluidity assays for detection of plasma membrane permeabilization and membrane dynamics, the present study demonstrated that valinomycin and cereulide exhibit antifungal activity against C. albicans and C. albidus by interrupting membrane-associated function. The mode of action of both valinomycin and cereulide are similar with that of AmB. Time-kill kinetics assay showed that valinomycin and cereulide exhibit fungistatic activity, whereas AmB features fungicidal activity. Additionally, the combination of compounds between each cyclic peptide and AmB reached maximal fungicidal activity more rapidly than AmB alone. This result corresponded with findings of scanning electron microscopy, fractional inhibitory concentration index and minimum fungicidal concentration (MFC)/MIC ratio, indicating that combinations of the drugs show synergistic effects for inhibiting the growth of these fungal strains. Sorbitol and ergosterol assays showed that both cyclic peptides affected cell wall and membrane components due to increases in MIC value, as observed in medium with sorbitol and ergosterol. Valinomycin and cereulide may promote permeability of fungal cell wall and cell membrane when used in combination with AmB. SN - 1773-0449 UR - https://www.unboundmedicine.com/medline/citation/29276078/Mode_of_action_and_synergistic_effect_of_valinomycin_and_cereulide_with_amphotericin_B_against_Candida_albicans_and_Cryptococcus_albidus_ DB - PRIME DP - Unbound Medicine ER -