Triclosan Demonstrates Synergic Effect with Amphotericin B and Fluconazole and Induces Apoptosis-Like Cell Death in Cryptococcus neoformans

Movahed, Elaheh; Tan, Guan Huat; Munusamy, Komathy; Yeow, Tee Cian; Tay, Sun Tee; Wong, Won Fen; Looi, Chung Yeng

doi:10.3389/fmicb.2016.00360

Cited by 28 publications

(15 citation statements)

References 77 publications

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“…This molecule showed in vitro synergistic activity with FLZ against C. albicans (Yu et al, 2011). Triclosan is also active against C. neoformans by activating the apoptosis pathway and also shows synergic activity with AmB and FLZ (Movahed et al, 2016). As ion homeostasis is a fundamental factor in the development of fungal disease, ion chelators have been used in the treatment of fungal infections.…”

Section: Drug Combinationsmentioning

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: Drug Combinationsmentioning

confidence: 99%

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

et al. 2017

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“…All antibiotics were obtained from Sigma-Aldrich China, Inc. Minimum inhibitory concentrations (MICs) were determined as specified by the Clinical and Laboratory Standards Institute standard M27-A3 document (Clinical and Laboratory Standards Institute, 2008), with modifications as described previously (Movahed et al, 2016). Following the manufacturer's instructions, stock solutions of FLU and MINO were dissolved with dimethyl sulfoxide (DMSO), and ampicillin was prepared in sterile distilled water.…”

Section: Strains Media and Antimicrobialsmentioning

confidence: 99%

“…The final drug concentrations in the wells ranged from 1-256 µg/ml for MINO and 0.25-256 µg/ml for FLU, RPMI-1640 medium was used as a negative control, and a drug-free well was set as the growth control. After 72 h of incubation at 35 • C, the MICs were determined by both visual reading and measurement of the optical density (OD) with a microplate reader at 562 nm (Movahed et al, 2016). The MICs were defined as the lowest concentration of drug that still enabled 80% of fungal growth inhibition compared with the drug-free control.…”

Section: Antifungal Activities Of Mino and Flumentioning

confidence: 99%

Minocycline and Fluconazole Have a Synergistic Effect Against Cryptococcus neoformans Both in vitro and in vivo

Kong

Cao

et al. 2020

Front. Microbiol.

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In recent decades, the incidence of Cryptococcus neoformans infection, which causes cryptococcosis, has consistently increased. Fluconazole (FLU) is frequently used in the treatment of this disease, mainly in the immunocompromised population, and longterm therapy usually produces drug resistance. Research on antifungal sensitizers has gained attention as a possible means of overcoming this drug resistance. Minocycline (MINO) has an inhibitory effect in vitro on FLU-resistant Candida albicans, and the combination of MINO and FLU has a synergistic effect on FLU-resistant C. albicans. A synergistic effect of MINO/FLU has been reported against C. neoformans, but this effect has not been evaluated on FLU-resistant isolates. This study aimed to investigate the interaction of MINO and FLU against FLU-resistant C. neoformans both in vitro and in vivo. We found that the combination of MINO and FLU had a synergistic effect on FLUresistant C. neoformans in vitro. For all FLU-resistant strains, the minimum inhibitory concentration (MIC) of FLU decreased significantly when used in combination with MINO, dropping from >128 µg/ml down to 4-8 µg/ml. Additionally, MINO and FLU had a synergistic effect on both susceptible and resistant C. neoformans biofilms, in which the MIC of FLU decreased from >256 µg/ml down to 4-16 µg/ml. Compared with FLU alone, the combination of MINO with FLU prolonged the survival rate of Galleria mellonella larvae infected with FLU-resistant C. neoformans, and also significantly decreased the fungal burden of infected larvae and reduced the tissue damage and destruction caused by FLU-resistant C. neoformans. These findings will contribute to the discovery of antifungal agents and may yield a new approach for the treatment of cryptococcosis caused by FLU-resistant C. neoformans.

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“…grubii (serotype A) H99 was obtained from American Type Culture Collection (ATCC). Environmental strains S48B, S68B and H4 were isolated from pigeon droppings, as described [ 28 , 29 ]. All cells were stored at − 80 °C freezer until usage.…”

Section: Methodsmentioning

confidence: 99%

Lung–infiltrating T helper 17 cells as the major source of interleukin-17A production during pulmonary Cryptococcus neoformans infection

et al. 2018

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BackgroundIL-17A has emerged as a key player in the pathologies of inflammation, autoimmune disease, and immunity to microbes since its discovery two decades ago. In this study, we aim to elucidate the activity of IL-17A in the protection against Cryptococcus neoformans, an opportunistic fungus that causes fatal meningoencephalitis among AIDS patients. For this purpose, we examined if C. neoformans infection triggers IL-17A secretion in vivo using wildtype C57BL/6 mice. In addition, an enhanced green fluorescence protein (EGFP) reporter and a knockout (KO) mouse models were used to track the source of IL-17A secretion and explore the protective function of IL-17A, respectively.ResultsOur findings showed that in vivo model of C. neoformans infection demonstrated induction of abundant IL-17A secretion. By examining the lung bronchoalveolar lavage fluid (BALF), mediastinal lymph node (mLN) and spleen of the IL-17A–EGFP reporter mice, we showed that intranasal inoculation with C. neoformans promoted leukocytes lung infiltration. A large proportion (~ 50%) of the infiltrated CD4+ helper T cell population secreted EGFP, indicating vigorous TH17 activity in the C. neoformans–infected lung. The infection study in IL-17A–KO mice, on the other hand, revealed that absence of IL-17A marginally boosted fungal burden in the lung and accelerated the mouse death.ConclusionTherefore, our data suggest that IL-17A is released predominantly from TH17 cells in vivo, which plays a supporting role in the protective immunity against C. neoformans infection.Electronic supplementary materialThe online version of this article (10.1186/s12865-018-0269-5) contains supplementary material, which is available to authorized users.

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Triclosan Demonstrates Synergic Effect with Amphotericin B and Fluconazole and Induces Apoptosis-Like Cell Death in Cryptococcus neoformans

Cited by 28 publications

References 77 publications

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

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

Minocycline and Fluconazole Have a Synergistic Effect Against Cryptococcus neoformans Both in vitro and in vivo

Lung–infiltrating T helper 17 cells as the major source of interleukin-17A production during pulmonary Cryptococcus neoformans infection

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