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重组内溶素作为抗耐药金黄色葡萄球菌的潜在疗法:研究现状和新的给药策略

发布者:抗性基因网 时间:2019-09-20 浏览量:1726

摘要

金黄色葡萄球菌(Staphylococcus aureus)是人和动物最常见的病原体之一,常常在皮肤和粘膜上定植。作为多种疾病的医院病原体和致病因子,它具有重要的临床意义。多药耐药菌株已变得越来越普遍,并且代表了发病率和死亡率的主要原因。因此,迫切需要新的对抗多药耐药病原体的策略。噬菌体衍生的酶,所谓的细胞内溶素和其他具有破坏细胞壁能力的肽聚糖水解酶代表了常规抗生素的可能替代品。这些裂解酶赋予高度宿主特异性并且可以替代或与抗生素组合使用,目的是特异性地治疗由革兰氏阳性耐药性细菌病原体如耐甲氧西林金黄色葡萄球菌引起的感染。 LysK是具有抗多种葡萄球菌物种活性的最佳特征性细胞内溶素之一。已经证明了进一步增强细胞内溶素的抗菌功效和适用性的各种方法。这些方法包括构建重组细胞内溶素衍生物和开发用于各种应用的新型递送策略,例如乳酸菌中细胞内溶素的产生及其与纳米颗粒的缀合。这些新颖的策略是本次审查的重点。


Staphylococcus aureus is one of the most common pathogens of humans and animals, where it frequently colonizes skin and mucosal membranes. It is of major clinical importance as a nosocomial pathogen and causative agent of a wide array of diseases. Multidrug-resistant strains have become increasingly prevalent and represent a leading cause of morbidity and mortality. For this reason, novel strategies to combat multidrug-resistant pathogens are urgently needed. Bacteriophage-derived enzymes, so-called endolysins, and other peptidoglycan hydrolases with the ability to disrupt cell walls represent possible alternatives to conventional antibiotics. These lytic enzymes confer a high degree of host specificity and could potentially replace or be utilized in combination with antibiotics, with the aim to specifically treat infections caused by Gram-positive drug-resistant bacterial pathogens such as methicillin-resistant S. aureus. LysK is one of the best-characterized endolysins with activity against multiple staphylococcal species. Various approaches to further enhance the antibacterial efficacy and applicability of endolysins have been demonstrated. These approaches include the construction of recombinant endolysin derivatives and the development of novel delivery strategies for various applications, such as the production of endolysins in lactic acid bacteria and their conjugation to nanoparticles. These novel strategies are a major focus of this review.


https://cmr.asm.org/content/31/1/e00071-17.short