Endolysins constitute a promising class of antibacterials against Gram-positive bacteria. Recently, endolysins have been engineered with selected peptides to obtain a new generation of lytic proteins, Artilysins, with specific activity against Gram-negative bacteria. Here, we demonstrate that artilysation can also be used to enhance the antibacterial activity of endolysins against Gram-positive bacteria and to reduce the dependence on external conditions. Art-240, a chimeric protein of the anti-streptococcal endolysin λSa2lys and the polycationic peptide PCNP, shows a similar species specificity as the parental endolysin, but the bactericidal activity against streptococci increases and is less affected by elevated NaCl concentrations and pH variations. Time-kill experiments and time-lapse microscopy demonstrate that the killing rate of Art-240 is approximately two-fold higher compared to wildtype endolysin λSa2lys, with a reduction in viable bacteria of 3 log units after 10 min. In addition, lower doses of Art-240 are required to achieve the same bactericidal effect.

中文翻译：

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内溶素λSa2lys的“ Artilysation”极大地提高了其对链球菌的酶促和抗菌活性。

内溶素构成了针对革兰氏阳性细菌的有前途的抗菌剂。最近，已经用选定的肽改造了细胞内溶素，以获得具有针对革兰氏阴性细菌的特异性活性的新一代裂解蛋白，Artilysins。在这里，我们证明了也可以使用artilysation增强内溶素对革兰氏阳性细菌的抗菌活性，并减少对外部条件的依赖性。Art-240是抗链球菌内溶素λSa2lys和聚阳离子肽PCNP的嵌合蛋白，显示出与亲本内溶素相似的物种特异性，但对链球菌的杀菌活性增加，并且不受NaCl浓度升高和pH变化的影响较小。时间杀灭实验和延时显微镜证明，Art-240的杀灭率比野生型溶细胞素λSa2lys高约2倍，存活细菌在10分钟后减少了3 log个单位。此外，需要较低剂量的Art-240即可达到相同的杀菌效果。