2.2. Phage-Derived Enzymes
2.2.噬菌体衍生酶
Another phage-related strategy already tested in animal models that has been proposed as an alternative to antibiotics is the use of phage-derived enzymes. Phages produce various types of enzymes capable of targeting specific bacteria [42]. Among other functions, some enzymes help them to penetrate the bacterial host and participate in bacterial lysis [21,43].
已经在动物模型中测试的另一种噬菌体相关策略已被提议作为抗生素的替代品，该策略是使用噬菌体衍生的酶。噬菌体产生能够靶向特定细菌的各种类型的酶[ 42]。在其他功能中，一些酶帮助它们穿透细菌宿主并参与细菌裂解[ 21，43]。
One of the most interesting types of phage-derived enzymes for therapy is lysins. Lysins are very specific enzymes that cleave peptidoglycan bonds and have a bactericidal effect on susceptible bacteria. Lysins are classified into two main groups: endolysins, which are involved in bacterial lysis, and virion-associated lysins (VALs), which are involved in entry into the host cell, allowing injection of the phage into it [42]. Endolysins are synthesized in the cytoplasm of infected bacteria to cause lysis. They are classified into canonical and exported endolysins. The canonical endolysins are considered the most interesting as enzybiotics and require other phage enzymes, the holins [43]. Lysins are especially useful in biofilm degradation [44]. They have been successfully tested in animal models against bacterial infections [45]. One example is the lysine LysSS, tested in a mouse model of systemic infection by A. baumannii, showing its potential to treat systemic infection [21,46].
用于治疗的最有趣的噬菌体衍生酶类型之一是溶素。赖氨酸是非常特异的酶，其裂解肽聚糖键并对敏感细菌具有杀菌作用。溶素分为两大类：内溶素，其参与细菌裂解，和病毒体相关溶素（VAL），其参与进入宿主细胞，允许将噬菌体注射到其中[ 42]。内溶素在感染细菌的细胞质中合成以引起溶解。它们被分类为典型的和输出的内溶素。典型的内溶素被认为是最令人感兴趣的酶制剂，并且需要其他噬菌体酶，holins [ 43]。赖氨酸在生物膜降解中特别有用[ 44]。它们已在动物模型中成功地进行了抗细菌感染的测试[ 45]。一个例子是赖氨酸LysSS，在A.鲍曼不动杆菌，显示其治疗全身感染的潜力[ 21，46]。
Holins are enzymes that also act in the lytic process involved in cell-wall degradation. When the concentration of holins exceeds a threshold, they form pores in the bacterial membrane and allow the action of endolysins. Holins are generalists and combine with other enzymes that broaden the spectrum of the host strain [21,47,48,49].
孔蛋白是也在涉及细胞壁降解的裂解过程中起作用的酶。当孔蛋白的浓度超过阈值时，它们在细菌膜中形成孔并允许内溶素的作用。洞蛋白是多面手，并且与拓宽宿主菌株谱的其他酶联合收割机结合[ 21，47，48，49]。
Depolymerases are phage-derived enzymes capable of degrading the extracellular substances that form the capsule of many bacteria [50]. There are several groups according to the type of bond they break [47]. Depolymerases have a broad host spectrum that contrasts with lysins, and they are also particularly useful in the elimination of biofilms [42,51]. For example, the effect of Dp42 depolymerase in the K. pneumoniae-infected mouse model has also been discussed recently. Dp42 increased the survival rate and significantly reduced the bacterial load in the liver, spleen, and lungs of the treated mouse [52].
解聚酶是噬菌体衍生的酶，能够降解形成许多细菌荚膜的细胞外物质[ 50]。有几个组根据他们打破键的类型[ 47]。解聚酶具有与溶素相反的宽宿主谱，并且它们在生物膜的消除中也特别有用[ 42，51]。例如，Dp42解聚酶在K.肺炎感染的小鼠模型最近也被讨论。Dp42增加了存活率，并显著降低了经处理小鼠肝、脾和肺中的细菌负荷[ 52]。
The creation and modification of phage proteins is also an interesting approach for the treatment of bacterial infections. Thanks to synthetic biology, bacterial spectrum proteins, bacterial resistance to them, and immunogenicity can be improved [21]. In addition, to reduce the emergence of resistance, an alternative solution would be to develop phage-derived enzyme cocktails.
噬菌体蛋白的产生和修饰也是治疗细菌感染的有趣方法。由于合成生物学，细菌谱蛋白，细菌对它们的抗性和免疫原性可以得到改善[ 21]。此外，为了减少耐药性的出现，另一种解决方案是开发噬菌体衍生的酶鸡尾酒。