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Mechanisms of Hop Inhibition Include the Transmembrane Redox Reaction

机译:啤酒花抑制的机制包括跨膜氧化还原反应

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In this work, a novel mechanistic model of hop inhibition beyond the proton ionophore action toward (beer spoiling) bacteria was developed. Investigations were performed with model systems using cyclic voltammetry for the determination of redox processes/conditions in connection with growth challenges with hop-sensitive and -resistant Lactobacillus brevis strains in the presence of oxidants. Cyclic voltammetry identified a transmembrane redox reaction of hop compounds at low pH (common in beer) and in the presence of manganese (present in millimolar levels in lactic acid bacteria). The antibacterial action of hop compounds could be extended from the described proton ionophore activity, lowering the intracellular pH, to pronounced redox reactivity, causing cellular oxidative damage. Accordingly, a correlation between the resistance of L. brevis strains to a sole oxidant to their resistance to hop could not be expected and was not detected. However, in connection with our recent study concerning hop ionophore properties and the resistance of hop-sensitive and -tolerant L. brevis strains toward proton ionophores (J. Behr and R. F. Vogel, J. Agric. Food Chem. 57:6074-6081, 2009), we suggest that both ionophore and oxidant resistance are required for survival under hop stress conditions and confirmed this correlation according to the novel mechanistic model. In consequence, the expression of several published hop resistance mechanisms involved in manganese binding/transport and intracellular redox balance, as well as that of proteins involved in oxidative stress under “highly reducing” conditions (cf. anaerobic cultivation and “antioxidative” hop compounds in the growth medium), is now comprehensible. Accordingly, hop resistance as a multifactorial dynamic property at least implies distinct resistance levels against two different mechanisms of hop inhibition, namely, proton ionophore-induced and oxidative stress-induced mechanisms. Beyond this specific model of hop inhibition, these investigations provide general insight on the role of electrophysiology and ion homeostasis in bacterial stress responses to membrane-active drugs.
机译:在这项工作中,开发了一种新的跃迁抑制机理模型,该跃迁抑制机理超越了质子离子载体对(啤酒变质)细菌的作用。使用循环伏安法的模型系统进行了研究,以确定在氧化剂存在下啤酒花敏感和耐药的短​​乳杆菌对生长挑战的氧化还原过程/条件。循环伏安法鉴定了啤酒花化合物在低pH(啤酒中常见)和锰(在乳酸菌中以毫摩尔水平存在)的跨膜氧化还原反应。啤酒花化合物的抗菌作用可以从所描述的质子离子载体活性(降低细胞内pH)扩展到明显的氧化还原反应性,从而引起细胞氧化损伤。因此,无法预期和未检测到短乳杆菌菌株对单一氧化剂的抗跳性的相关性。但是,结合我们最近关于啤酒花离子载体性质以及对啤酒花敏感和耐受的短螺旋乳杆菌菌株对质子离子载体的抗性的研究(J. Behr和RF Vogel,J。Agric。Food Chem。57:6074-6081, 2009),我们认为,在啤酒花胁迫条件下的生存需要离子载体和抗氧化剂,并根据新型机理模型证实了这种相关性。结果,涉及锰结合/转运和细胞内氧化还原平衡的几种已公开的啤酒花抗性机制的表达,以及在“高度还原”条件下与氧化应激有关的蛋白质的表达(参见厌氧培养和“抗氧化”啤酒花化合物)。现在可以理解。因此,作为多因素动态特性的啤酒花抗性至少意味着对啤酒花抑制的两种不同机理,即质子离子载体诱导的和氧化应激诱导的机理的不同的抗性水平。除了这种特定的跃点抑制模型之外,这些研究还提供了有关电生理和离子稳态在细菌对膜活性药物的应激反应中的作用的一般见解。

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