Triclosan inhibition of membrane enzymes and glycolysis of Streptococcus mutans in suspensions and biofilms
Triclosan inhibition of membrane enzymes and glycolysis of Streptococcus mutans in suspensions and biofilms
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DOI：
10.1139/w06-055
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发表时间：
2006-10-01
影响因子：
2.8
通讯作者：
Marquis, Robert E.
中科院分区：
文献类型：
--
作者：
Phan, Tuan-Nghia;Marquis, Robert E.
三氯生被发现是口腔病原体变形链球菌的F（H+）-ATP酶的有效抑制剂，并增加完整细胞的质子渗透性。此外，它与弱酸性跨膜质子载体，如氟化物或山梨酸盐，增敏糖酵解酸抑制。即使在中性pH值下，三氯生也可以作为糖酵解酶丙酮酸激酶、乳酸脱氢酶、醛缩酶和磷酸烯醇式丙酮酸：糖磷酸转移酶系统（PTS）的不可逆抑制剂，更直接地抑制糖酵解。三氯生浓度约为0.1 mmol/L，pH值为7时，约为S.悬浮液中的变形细胞。完整生物膜中的细胞对三氯生抑制糖酵解的敏感性几乎与悬浮液中的细胞一样，但对杀死的抵抗力更强。糖酵解的不可逆抑制靶点包括PTS和细胞质酶，特别是丙酮酸激酶、乳酸脱氢酶，以及在较小程度上的醛缩酶。一般结论是，三氯生是变形链球菌的多靶点抑制剂，其缺乏三氯生敏感的FabI烯酰-ACP还原酶，并且在初次或重复暴露后保留三氯生的牙菌斑生物膜中抑制糖酵解将降低致龋性。
Triclosan was found to be a potent inhibitor of the F(H+)-ATPase of the oral pathogen Streptococcus mutans and to increase proton permeabilities of intact cells. Moreover, it acted additively with weak-acid transmembrane proton carriers, such as fluoride or sorbate, to sensitize glycolysis to acid inhibition. Even at neutral pH, triclosan could inhibit glycolysis more directly as an irreversible inhibitor of the glycolytic enzymes pyruvate kinase, lactic dehydro genase, aldolase, and the phosphoenolpyruvate:sugar phosphotransferase system (PTS). Cell glycolysis in suspensions or biofilms was inhibited in a pH-dependent manner by triclosan at a concentration of about 0.1 mmol/L at pH 7, approximately the lethal concentration for S. mutans cells in suspensions. Cells in intact biofilms were almost as sensitive to triclosan inhibition of glycolysis as were cells in suspensions but were more resistant to killing. Targets for irreversible inhibition of glycolysis included the PTS and cytoplasmic enzymes, specifically pyruvate kinase, lactic dehydrogenase, and to a lesser extent, aldolase. General conclusions are that triclosan is a multi-target inhibitor for mutans streptococci, which lack a triclosan-sensitive FabI enoyl-ACP reductase, and that inhibition of glycolysis in dental plaque biofilms, in which triclosan is retained after initial or repeated exposure, would reduce cariogenicity.