細(xì)菌素
細(xì)菌素是細(xì)菌在代謝過程中通過核糖體合成的一類具有抑菌活性的多肽或前體多肽,在一定的濃度下具有顯著的抗菌活性[1]。細(xì)菌素因其具有天然無危害、不易產(chǎn)生耐藥性、有較好的抑菌效果等特點而被受關(guān)注,細(xì)菌素將是抗生素的有力替代者[2]。
細(xì)菌素的分類
細(xì)菌素根據(jù)其分子量、熱穩(wěn)定性、酶的敏感性、作用模式和翻譯后修飾氨基酸的存在進(jìn)行分類。按照分子量可將革蘭氏陰性菌的細(xì)菌素分為大腸桿菌素(colicins)和小菌素(microcins)兩類,是從大腸桿菌和其他腸桿菌中分離出來的[3]。革蘭氏陽性菌與革蘭氏陰性菌都可以更進(jìn)一步分出亞群[4],革蘭氏陽性菌的細(xì)菌素可分成三大類[5],即Ⅰ類翻譯后修飾的羊毛硫細(xì)菌素(lantibiotics)、Ⅱ類翻譯后未修飾的非羊毛硫型細(xì)菌素(unlantibi-otic)、Ⅲ類大分子熱不穩(wěn)定的蛋白質(zhì)類細(xì)菌素(heat unstable)。
細(xì)菌素以多種機(jī)制抑制細(xì)菌生長。抑菌的機(jī)制可劃分為細(xì)胞膜的作用機(jī)制和細(xì)胞內(nèi)外基質(zhì)的作用機(jī)制。
細(xì)菌素通常具有雙親性結(jié)構(gòu)并帶有正電荷,便于結(jié)合到靶細(xì)胞膜發(fā)揮作用,靶細(xì)胞膜在細(xì)菌素的作用下形成孔洞,細(xì)胞內(nèi)離子和小分子外流,細(xì)胞內(nèi)外的質(zhì)子動能和電勢差消失,靶細(xì)胞在恢復(fù)質(zhì)子動能和電勢差的過程中耗盡三磷酸腺苷 (ATP) 而被殺滅[6]。
細(xì)菌素也可以通過細(xì)胞膜進(jìn)入靶細(xì)胞內(nèi),抑制蛋白質(zhì)的合成、核酸的復(fù)制或轉(zhuǎn)錄[7]。nisin誘導(dǎo)靶細(xì)胞自溶酶的釋放和激活,造成靶細(xì)胞自溶,或是與肽聚糖合成前體結(jié)合,阻止細(xì)胞壁形成,mersacidin也通過抑制細(xì)胞壁的合成發(fā)揮抗菌效果[8]。lactocillin、microcinB17、microcin J25分別抑制靶細(xì)胞蛋白質(zhì)合成、DNA 復(fù)制和 RNA 聚合酶活性[9-11]。
枯草芽孢桿菌素 A32 使靶細(xì)胞無法進(jìn)行正常的磷代謝,細(xì)胞壁和細(xì)胞膜受損,內(nèi)容物外泄,蛋白質(zhì)的表達(dá)也受到影響[12]。雙歧桿菌細(xì)菌素 bifidocin A 增加了金黃色葡萄球菌的細(xì)胞膜通透性,造成鉀離子、無機(jī)磷離子和ATP 分子的泄露[13]。sakacin ZFM225 破壞了李斯特菌細(xì)胞壁的完整性,并阻止了脂Ⅱ分子的合成[14]。
細(xì)菌素是動物生產(chǎn)中抗生素的潛在替代品并得到廣泛應(yīng)用[15]。Ustundag A等[16] 通過實驗發(fā)現(xiàn)將有機(jī)酸和細(xì)菌素通過組合的形式聯(lián)合控制飼料中的單增李斯特菌有著非常好的效果;在飼料中添加可抑制豬腸道大腸桿菌繁殖的細(xì)菌素大腸菌素 E(colicin E1)[17] 能夠減少由大腸桿菌產(chǎn)腸毒素菌株所誘發(fā)的斷乳后拉肚子的發(fā)病率和嚴(yán)重性,從而提高了母豬的正常繁殖性能[18]。
Nocek J E 等[19] 的研究表明,通過加入含屎腸球菌和酵母菌等復(fù)合微生態(tài)制劑,在產(chǎn)犢前后的奶牛飼糧中可增加其采食量和產(chǎn)乳量。細(xì)菌素對引起奶牛乳房炎的病原菌有較強(qiáng)的抗菌活性,可以減少乳房炎的發(fā)病率[20]。nisin處理奶牛乳頭減少了乳頭表面葡萄球菌、鏈球菌和總細(xì)菌數(shù)量,而且與羅伊氏菌素有較強(qiáng)的協(xié)同效果[21]。
陳曉生等[22] 發(fā)現(xiàn)在鴨料中加入蠶抗微生物肽 AD飼喂肉鴨時,會促進(jìn)肉鴨的成長,從而減少腹脂率、增加產(chǎn)肉率。黃自然等[23] 在對蝦飼料中加入了含量約為 2-4mg/kg 的抗菌肽,再飼喂南美白對蝦,可以增加對蝦的成活率、增長率。同時,細(xì)菌素也成為動物飼料中動物生長促進(jìn)劑(AGP)的理想替代品。研究表明,飼養(yǎng)微生物(益生菌 LAB)可顯著增加動物的體重[24],這是因為產(chǎn)生細(xì)菌素的 LAB 可以用來調(diào)節(jié)腸道微生物群,從而提高飼料效率。目前,細(xì)菌素在飼料應(yīng)用中通過包埋來保護(hù)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,飼喂小鼠飼料后,在糞便中檢測到的Nisin 活性[26-27]。
細(xì)菌素是細(xì)菌在代謝過程中通過核糖體合成的一類具有抑菌活性的多肽或前體多肽,對金黃色葡萄球菌等多種致病菌具有良好的抗菌活性。隨著分子生物學(xué)的深入發(fā)展和基因工程的不斷成熟,細(xì)菌素的應(yīng)用潛力也將不斷提高。未來細(xì)菌素在預(yù)防和治療動物疾病、改善動物機(jī)體健康、提高生產(chǎn)性能等方面將會發(fā)揮更大的作用。
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