New insights into the mode of action of the lantibiotic salivaricin B.
New insights into the mode of action of the lantibiotic salivaricin B.
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DOI：
10.1038/srep31749
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发表时间：
2016-08-16
影响因子：
4.6
通讯作者：
Philip K
中科院分区：
文献类型：
--
作者：
Barbour A;Tagg J;Abou-Zied OK;Philip K
唾液毒素B是一种由25个氨基酸组成的多环肽，属于AII型抗生素，最早由唾液链球菌产生。在这项研究中，我们描述了唾液毒素B对易感革兰氏阳性细菌的杀菌模式。唾液毒苷B的杀伤作用需要微摩尔浓度的乳酸链球菌素，而乳酸链球菌素A的原型在纳米摩尔水平上被证明是有效的。与nisin A不同，salivaricin B在易感细胞中不会诱导孔形成或消散膜电位。这是通过测量唾液毒苷B与细菌膜囊泡相互作用时17位色氨酸残基的荧光来建立的。荧光蓝移的缺失表明唾液毒苷B未能穿透细胞膜。另一方面，唾液苷B干扰细胞壁的生物合成，这可以从最终可溶性细胞壁前体udp - murnac -五肽的积累中看出，udp - murnac -五肽是细菌肽聚糖的主干。唾液毒苷b处理的细胞透射电镜显示细胞壁厚度减少，并有异常隔膜形成的迹象，但细胞质膜完整性未见明显变化。
Salivaricin B is a 25 amino acid polycyclic peptide belonging to the type AII lantibiotics and first shown to be produced by Streptococcus salivarius. In this study we describe the bactericidal mode of action of salivaricin B against susceptible Gram-positive bacteria. The killing action of salivaricin B required micro-molar concentrations of lantibiotic whereas the prototype lantibiotic nisin A was shown to be potent at nano-molar levels. Unlike nisin A, salivaricin B did not induce pore formation or dissipate the membrane potential in susceptible cells. This was established by measuring the fluorescence of the tryptophan residue at position 17 when salivaricin B interacted with bacterial membrane vesicles. The absence of a fluorescence blue shift indicates a failure of salivaricin B to penetrate the membranes. On the other hand, salivaricin B interfered with cell wall biosynthesis, as shown by the accumulation of the final soluble cell wall precursor UDP-MurNAc-pentapeptide which is the backbone of the bacterial peptidoglycan. Transmission electron microscopy of salivaricin B-treated cells showed a reduction in cell wall thickness together with signs of aberrant septum formation in the absence of visible changes to cytoplasmic membrane integrity.