The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation
The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation
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DOI：
10.1111/j.1432-1033.1997.t01-1-00193.x
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发表时间：
1997-05-15
期刊：
影响因子：
--
通讯作者：
Sahl, HG
中科院分区：
文献类型：
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作者：
Brotz, H;Bierbaum, G;Sahl, HG
此前有报道称，抗生素mersacidin会干扰细菌肽聚糖的生物合成[Brotz， H., Bierbaum， G., Markus， A., Molitor， E. & Sahl， H.-G.]。(1995) Antimicrob。[j].中国生物医学工程学报，2014,33(2):444 - 444。在这里，我们将重点放在目标反应上，并描述了mersacidin诱导的udp - n-乙酰muramyl -五肽的积累，这表明在细胞质前体形成后，抑制了肽聚糖的合成。涉及巨型芽孢杆菌KM的壁膜颗粒部分的体外研究表明，mersacidin并不能阻止脂质II[十一戊烯基-二磷酸基- n -乙酰muramoyl-（五肽）- n -乙酰氨基葡萄糖]的合成，但特别是随后通过转糖基化将该中间体转化为聚合的新生聚糖链。与其他转糖基化抑制剂的比较表明，mersacidin的体外有效浓度在糖肽类抗生素万古霉素的范围内，但比竞争酶抑制剂莫诺霉素高出2-3个数量级。与糖肽的类比可能暗示灭精蛋白与肽聚糖前体而不是与酶相互作用。然而，与万古霉素不同，mersacidin抑制udp - n - acetylmuram酰三肽形成肽聚糖，并对表达vanA抗性基因簇的屎肠球菌有活性。这说明mersacidin与万古霉素的分子靶点不同，两种抗生素之间不存在交叉耐药。
The lantibiotic mersacidin has been previously reported to interfere with bacterial peptidoglycan biosynthesis, [Brotz, H., Bierbaum, G., Markus, A., Molitor, E. & Sahl, H.-G. (1995) Antimicrob. Agents Chemother. 39, 714-719]. Here, we focus on the target reaction and describe a mersacidin-induced accumulation of UDP-N-acetylmuramoyl-pentapeptide, indicating that inhibition of peptidoglycan synthesis occurs after the formation of cytoplasmic precursors. In vitro studies involving a wall-membrane particulate fraction of Bacillus megaterium KM demonstrated that mersacidin did not prevent the synthesis of lipid II [undecaprenyl-diphosphoryl-N-acetylmuramoyl-(pentapeptide)-N-acetylglucosamine] but specifically the subsequent conversion of this intermediate into polymeric nascent glycan strands by transglycosylation. Comparison with other inhibitors of transglycosylation shows that the effective concentration of mersacidin in vitro is in the range of that of the glycopeptide antibiotic vancomycin but 2-3 orders of magnitude higher than that of the competitive enzyme inhibitor moenomycin. The analogy to the glycopeptides may hint at an interaction of mersacidin with the peptidoglycan precursor rather than with the enzyme. Unlike vancomycin however, mersacidin inhibits peptidoglycan formation from UDP-N-acetylmuramoyl-tripeptide and is active against Enterococcus faecium expressing the vanA resistance gene cluster. This indicates that the molecular target site of mersacidin differs from that of vancomycin and that no cross-resistance exists between the two antibiotics.