Novel Chimerical Endolysins with Broad Antimicrobial Activity Against Methicillin-Resistant Staphylococcus aureus
Novel Chimerical Endolysins with Broad Antimicrobial Activity Against Methicillin-Resistant Staphylococcus aureus
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DOI：
10.1089/mdr.2012.0025
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发表时间：
2012-06-01
影响因子：
2.6
通讯作者：
Sao-Jose, Carlos
中科院分区：
文献类型：
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作者：
Fernandes, Sofia;Proenca, Daniela;Sao-Jose, Carlos
由于其细菌裂解作用，噬菌体内溶素作为一种潜在的抗生素替代品，在与革兰氏阳性致病菌的战斗中，特别是那些表现出多药耐药性的致病菌，最近受到了广泛的关注。然而，内溶素的大规模生产和纯化由于其溶解度低而经常受到损害。此外，与噬菌体感染时的作用相比，大量的内溶素似乎表现出较低的溶解效果。在这里，我们利用最近发现的两种肠球菌内溶素的高溶解度来构建靶向金黄色葡萄球菌的嵌合体。这些内溶素的假定细胞壁结合区域被葡萄球菌内溶素取代，显示出较差的溶解度。在适当的条件下，嵌合体表现出亲本肠球菌内溶素的高溶解度。此外，它们被证明对一系列最相关的耐甲氧西林金黄色葡萄球菌流行病克隆和其他革兰氏阳性病原体具有广泛的活性。因此，融合异种来源的内溶素结构域似乎是一种合适的方法来设计新的有效的内溶素，这些内溶素具有改变和/或扩展的裂解谱，适合大规模生产。
Due to their bacterial lytic action, bacteriophage endolysins have recently gained great attention as a potential alternative to antibiotics in the combat of Gram-positive pathogenic bacteria, particularly those displaying multidrug resistance. However, large-scale production and purification of endolysins is frequently impaired due to their low solubility. In addition, a large number of endolysins appear to exhibit reduced lytic efficacy when compared with their action during phage infection. Here, we took advantage of the high solubility of two recently characterized enterococcal endolysins to construct chimeras targeting Staphylococcus aureus. The putative cell wall binding domain of these endolysins was substituted by that of a staphylococcal endolysin that showed poor solubility. Under appropriate conditions the resulting chimeras presented the high solubility of the parental enterococcal endolysins. In addition, they proved to be broadly active against a collection of the most relevant methicillin-resistant S. aureus epidemic clones and against other Gram-positive pathogens. Thus, fusion of endolysin domains of heterologous origin seems to be a suitable approach to design new potent endolysins with changed and/or extended lytic spectrum that are amenable to large-scale production.