The effects of parabens on the mechanosensitive channels of E. coli
The effects of parabens on the mechanosensitive channels of E. coli
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DOI：
10.1007/s00249-005-0468-x
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发表时间：
2005-07-01
影响因子：
2
通讯作者：
Martinac, B
中科院分区：
文献类型：
--
作者：
Nguyen, T;Clare, B;Martinac, B
对羟基苯甲酸酯是对羟基苯甲酸的烷基酯，在广泛的食品、药品和化妆品中用作防腐剂(Soni等人。食品化学。托昔康。39：513-532,2001)。尽管它们已经共同使用了50多年，但它们的作用机制仍然不清楚。在这项研究中，我们考察了乙基和丙基对羟基苯甲酸乙酯和丙基对羟基苯甲酸乙酯对重组为唑连素脂质体的大肠杆菌大电导机械敏感通道(MSCL)门控的影响。我们发现丙基和对羟基苯甲酸乙酯自发地激活了MSCL。此外，添加对羟基苯甲酸丙酯导致MSCL活性增加和P-1/2降低，P-1/2、50%的时间打开MSCL的压力、打开MSCL所需的自由能以及描述通道对压力的敏感性的参数a降低。此外，在计算机方面的研究表明，对羟基苯甲酸丙酯与MSCL的通道门结合。机械敏感的小电导通道也被对羟基苯甲酸酯自发激活。综上所述，我们的研究表明，以前未知的对羟基苯甲酸酯作为抗菌剂的作用机制之一是通过与机械敏感通道的相互作用来扰乱细菌的渗透梯度。
Parabens are alkyl esters of p-hydroxybenzoic acid used as preservatives in a wide range of food, pharmaceutical, and cosmetic products (Soni et al. Food Chem. Toxicol. 39:513-532, 2001). Despite their common use for over 50 years, their mechanism of action is still unclear. In this study we examined the effects of ethyl and propyl paraben, on gating of the E. coli mechanosensitive channel of large conductance (MscL) reconstituted into azolectin liposomes. We found that propyl and ethyl paraben spontaneously activate MscL. Moreover, the addition of propyl paraben caused an increase in MscL activity and the lowering Of P-1/2, the pressure at which the MscL was opened 50% of the time, the AGO, the free energy required to open the MscL, and the parameter a, which describes the channel sensitivity to pressure. In addition, in silico studies showed that propyl paraben binds to the channel gate of the MscL. The mechanosensitive channel of small conductance was also found to be spontaneously activated by parabens. In summary, our study indicates that one of the previously unidentified mechanisms of action of parabens as antimicrobial agents is via an interaction with the mechanosensitive channels to upset the osmotic gradients in bacteria.