Potentiated inhibition of Trichoderma virens and other environmental fungi by new biocide combinations.

Potentiated inhibition of Trichoderma virens and other environmental fungi by new biocide combinations.
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DOI:
10.1007/s00253-021-11211-3
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发表时间:
2021-04
影响因子:
5
通讯作者:
Avery SV
Avery SV
中科院分区:
工程技术2区
文献类型:
--
作者:
Vallières C;Alexander C;Avery SV

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真菌引起各种严重的社会经济问题,包括有价值的产品和材料的生物退化,在全球范围内产生了价值约110亿美元的生物杀灭剂行业。为了帮助对抗通常在材料产品中定植的环境真菌,本研究测试了一种经批准的杀真菌剂与FDA(食品和药物管理局)批准的多种药剂的组合可以揭示具有杀真菌应用前景的有效组合活性的假设。使用获批化合物的策略降低了任何有效组合的潜在开发风险。对1280种FDA批准的化合物进行了高通量测定,以发现那些增强碘代丙炔基丁基氨基甲酸酯(IPBC)对绿木霉生长的影响的化合物; IPBC是两种最广泛使用的生物杀灭剂产品法规批准的杀真菌剂之一。从该文库中,34种化合物与IPBC组合强烈抑制真菌生长。对其他环境真菌进行了测试,这些真菌是合成材料对真菌定殖的抗性的标准生物标志物。三氟拉嗪(TFZ)与IPBC的组合增强了五种测试真菌中的三种的生长抑制。抗真菌剂海克替丁(HEX)增强了IPBC对两种试验微生物的作用。这些组合行动的机制上的可检验的假设进行了讨论。IPBC + TFZ和IPBC + HEX均未表现出针对哺乳动物细胞的组合效应。这些组合在掺入具有杀真菌剂递送潜力的聚合物基质(藻酸盐)后保留了强的真菌生长抑制特性。该研究揭示了这种批准的化合物在控制真菌环境机会中用于新的组合应用的潜力。·使用已批准的杀真菌剂进行搜索,以在药物库中找到新的杀真菌协同作用。·新的组合抑制不同基质上关键环境真菌的生长。·该方法能够更快速地响应对新杀菌剂的需求。在线版本包含补充材料,可通过10.1007/s00253 - 021 - 11211 - 3获得。
Fungi cause diverse, serious socio-economic problems, including biodeterioration of valuable products and materials that spawns a biocides industry worth ~$11 billion globally. To help combat environmental fungi that commonly colonise material products, this study tested the hypothesis that combination of an approved fungicide with diverse agents approved by the FDA (Food and Drug Administration) could reveal potent combinatorial activities with promise for fungicidal applications. The strategy to use approved compounds lowers potential development risks for any effective combinations. A high-throughput assay of 1280 FDA-approved compounds was conducted to find those that potentiate the effect of iodopropynyl-butyl-carbamate (IPBC) on the growth of Trichoderma virens; IPBC is one of the two most widely used Biocidal Products Regulations–approved fungicides. From this library, 34 compounds in combination with IPBC strongly inhibited fungal growth. Low-cost compounds that gave the most effective growth inhibition were tested against other environmental fungi that are standard biomarkers for resistance of synthetic materials to fungal colonisation. Trifluoperazine (TFZ) in combination with IPBC enhanced growth inhibition of three of the five test fungi. The antifungal hexetidine (HEX) potentiated IPBC action against two of the test organisms. Testable hypotheses on the mechanisms of these combinatorial actions are discussed. Neither IPBC + TFZ nor IPBC + HEX exhibited a combinatorial effect against mammalian cells. These combinations retained strong fungal growth inhibition properties after incorporation to a polymer matrix (alginate) with potential for fungicide delivery. The study reveals the potential of such approved compounds for novel combinatorial applications in the control of fungal environmental opportunists. • Search with an approved fungicide to find new fungicidal synergies in drug libraries. • New combinations inhibit growth of key environmental fungi on different matrices. • The approach enables a more rapid response to demand for new biocides. The online version contains supplementary material available at 10.1007/s00253-021-11211-3.
DOI: 10.1371/journal.pgen.1000151
发表时间: 2008-08-08
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影响因子: 4.5
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