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「微小但强大」:探秘细菌素的神奇作用机制
来源: | 作者:上海嘉冠 | 发布时间: 2024-02-01 | 575 次浏览 | 分享到:



细菌素



细菌素是细菌在代谢过程中通过核糖体合成的一类具有抑菌活性的多肽或前体多肽,在一定的浓度下具有显著的抗菌活性[1]。细菌素因其具有天然无危害、不易产生耐药性、有较好的抑菌效果等特点而被受关注,细菌素将是抗生素的有力替代者2


细菌素的分类


细菌素根据其分子量、热稳定性、酶的敏感性、作用模式和翻译后修饰氨基酸的存在进行分类。按照分子量可将革兰氏阴性菌的细菌素分为大肠杆菌素(colicins)和小菌素(microcins)两类,是从大肠杆菌和其他肠杆菌中分离出来的3]。革兰氏阳性菌与革兰氏阴性菌都可以更进一步分出亚群4],革兰氏阳性菌的细菌素可分成三大类5],即Ⅰ类翻译后修饰的羊毛硫细菌素(lantibiotics)、Ⅱ类翻译后未修饰的非羊毛硫型细菌素(unlantibi-otic)、Ⅲ类大分子热不稳定的蛋白质类细菌素(heat unstable)。



细菌素的作用机制

细菌素以多种机制抑制细菌生长。抑菌的机制可划分为细胞膜的作用机制和细胞内外基质的作用机制。


细菌素通常具有双亲性结构并带有正电荷,便于结合到靶细胞膜发挥作用,靶细胞膜在细菌素的作用下形成孔洞,细胞内离子和小分子外流,细胞内外的质子动能和电势差消失,靶细胞在恢复质子动能和电势差的过程中耗尽三磷酸腺苷 (ATP) 而被杀灭[6]


细菌素也可以通过细胞膜进入靶细胞内,抑制蛋白质的合成、核酸的复制或转录[7]。nisin诱导靶细胞自溶酶的释放和激活,造成靶细胞自溶,或是与肽聚糖合成前体结合,阻止细胞壁形成,mersacidin也通过抑制细胞壁的合成发挥抗菌效果[8]。lactocillin、microcinB17、microcin J25分别抑制靶细胞蛋白质合成、DNA 复制和 RNA 聚合酶活性[9-11]


枯草芽孢杆菌素 A32 使靶细胞无法进行正常的磷代谢,细胞壁和细胞膜受损,内容物外泄,蛋白质的表达也受到影响[12]。双歧杆菌细菌素 bifidocin A 增加了金黄色葡萄球菌的细胞膜通透性,造成钾离子、无机磷离子和ATP 分子的泄露[13]。sakacin ZFM225 破坏了李斯特菌细胞壁的完整性,并阻止了脂Ⅱ分子的合成[14]


细菌素在养殖生产中的应用

细菌素是动物生产中抗生素的潜在替代品并得到广泛应用[15]。Ustundag A等[16] 通过实验发现将有机酸和细菌素通过组合的形式联合控制饲料中的单增李斯特菌有着非常好的效果;在饲料中添加可抑制猪肠道大肠杆菌繁殖的细菌素大肠菌素 E(colicin E1)[17] 能够减少由大肠杆菌产肠毒素菌株所诱发的断乳后拉肚子的发病率和严重性,从而提高了母猪的正常繁殖性能[18]


Nocek J E 等[19] 的研究表明,通过加入含屎肠球菌和酵母菌等复合微生态制剂,在产犊前后的奶牛饲粮中可增加其采食量和产乳量。细菌素对引起奶牛乳房炎的病原菌有较强的抗菌活性,可以减少乳房炎的发病率[20]。nisin处理奶牛乳头减少了乳头表面葡萄球菌、链球菌和总细菌数量,而且与罗伊氏菌素有较强的协同效果[21]


陈晓生等[22] 发现在鸭料中加入蚕抗微生物肽 AD饲喂肉鸭时,会促进肉鸭的成长,从而减少腹脂率、增加产肉率。黄自然等[23] 在对虾饲料中加入了含量约为 2-4mg/kg 的抗菌肽,再饲喂南美白对虾,可以增加对虾的成活率、增长率。同时,细菌素也成为动物饲料中动物生长促进剂(AGP)的理想替代品。研究表明,饲养微生物(益生菌 LAB)可显著增加动物的体重[24],这是因为产生细菌素的 LAB 可以用来调节肠道微生物群,从而提高饲料效率。目前,细菌素在饲料应用中通过包埋来保护其生物活性[25]。Nisin A 被包裹在介孔材料中,防止胃蛋白酶和胰蛋白酶的降解,饲喂小鼠饲料后,在粪便中检测到的Nisin 活性[26-27]


细菌素是细菌在代谢过程中通过核糖体合成的一类具有抑菌活性的多肽或前体多肽,对金黄色葡萄球菌等多种致病菌具有良好的抗菌活性。随着分子生物学的深入发展和基因工程的不断成熟,细菌素的应用潜力也将不断提高。未来细菌素在预防和治疗动物疾病、改善动物机体健康、提高生产性能等方面将会发挥更大的作用。

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