Transcriptome analysis reveals mechanisms by which Lactococcus lactis acquires nisin resistance
Transcriptome analysis reveals mechanisms by which Lactococcus lactis acquires nisin resistance
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DOI：
10.1128/aac.50.5.1753-1761.2006
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发表时间：
2006-05-01
影响因子：
4.9
通讯作者：
Kuipers, OP
中科院分区：
文献类型：
--
作者：
Kramer, NE;Van Hijum, SAFT;Kuipers, OP
乳链菌肽是由乳酸乳球菌产生的一种后修饰抗菌肽，被广泛用作食品防腐剂。然而，导致细菌中乳链菌肽抗性发展的机制知之甚少。我们使用L.乳酸链球菌IL 1403的表达，以鉴定获得性乳链菌肽抗性机制的潜在因素。对L. lactis IL 1403和L.乳酸链球菌IL 1403 NiSr，其达到75倍更高的乳链菌肽抗性水平。在编码参与细胞壁生物合成、能量代谢、脂肪酸和磷脂代谢、调节功能以及金属和/或肽转运和结合的蛋白质的基因中观察到差异表达。这些结果进一步证实了这些基因的几个敲除和过表达突变体强烈改变了乳链菌肽的抗性水平，一些敲除菌株不能再对与野生型菌株相同水平的乳链菌肽产生抗性。乳酸链球菌获得性耐药机制的研究。乳酸是复杂的，涉及各种不同的机制。这四种主要机制是（i）防止乳链菌肽到达细胞质膜，（ii）降低细胞外介质的酸度，从而刺激乳链菌肽与细胞壁的结合，（iii）防止乳链菌肽插入细胞膜，以及（iv）可能将乳链菌肽转运穿过细胞膜或将乳链菌肽挤出细胞膜。
Nisin, a posttranslationally modified antimicrobial peptide produced by Lactococcus lactis, is widely used as a food preservative. Yet, the mechanisms leading to the development of nisin resistance in bacteria are poorly understood. We used whole-genome DNA microarrays of L. lactis IL1403 to identify the factors underlying acquired nisin resistance mechanisms. The transcriptomes of L. lactis IL1403 and L. lactis IL1403 NiSr, which reached a 75-fold higher nisin resistance level, were compared. Differential expression was observed in genes encoding proteins that are involved in cell wall biosynthesis, energy metabolism, fatty acid and phospholipid metabolism, regulatory functions, and metal and/or peptide transport and binding. These results were further substantiated by showing that several knockout and overexpression mutants of these genes had strongly altered nisin resistance levels and that some knockout strains could no longer become resistant to the same level of nisin as that of the wild-type strain. The acquired nisin resistance mechanism in L. lactis is complex, involving various different mechanisms. The four major mechanisms are (i) preventing nisin from reaching the cytoplasmic membrane, (ii) reducing the acidity of the extracellular medium, thereby stimulating the binding of nisin to the cell wall, (iii) preventing the insertion of nisin into the membrane, and (iv) possibly transporting nisin across the membrane or extruding nisin out of the membrane.