For bacteriophage infections, the cell walls of bacteria, consisting of a single highly polymeric molecule of peptidoglycan (PG), pose a major problem for the release of progeny virions. Phage lysis proteins that overcome this barrier can point the way to new antibacterial strategies ¹ , especially small lytic single-stranded DNA (the microviruses) and RNA phages (the leviviruses) that effect host lysis using a single non-enzymatic protein ² . Previously, the A₂ protein of levivirus Qβ and the E protein of the microvirus ϕX174 were shown to be 'protein antibiotics' that inhibit the MurA and MraY steps of the PG synthesis pathway ^2-4 . Here, we investigated the mechanism of action of an unrelated lysis protein, Lys^M, of the Escherichia coli levivirus M ⁵ . We show that Lys^M inhibits the translocation of the final lipid-linked PG precursor called lipid II across the cytoplasmic membrane by interfering with the activity of MurJ. The finding that Lys^M inhibits a distinct step in the PG synthesis pathway from the A₂ and E proteins indicates that small phages, particularly the single-stranded RNA (ssRNA) leviviruses, have a previously unappreciated capacity for evolving novel inhibitors of PG biogenesis despite their limited coding potential.

中文翻译：

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病毒蛋白抗生素抑制脂质II脂酶的活性。

对于噬菌体感染，由单个高度聚合的肽聚糖（PG）分子组成的细菌细胞壁是释放子代病毒体的主要问题。克服这一障碍的噬菌体裂解蛋白可以为新的抗菌策略指明道路¹，特别是小的裂解单链DNA（微病毒）和RNA噬菌体（左旋病毒），它们会使用单个非酶蛋白^2进行宿主裂解。以前，鼠病毒Qβ的A ₂蛋白和微小病毒ϕX174的E蛋白被证明是“蛋白抗生素”，可以抑制PG合成途径^2-4的MurA和MraY步骤。在这里，我们研究了不相关的裂解蛋白Lys ^M的作用机理。，大肠杆菌的左旋病毒M ⁵。我们表明Lys ^M通过干扰MurJ的活性抑制了最终的脂质连接的PG前体，称为脂质II，跨细胞质膜的转运。Lys ^M抑制了A ₂和E蛋白在PG合成途径中一个明显步骤的发现表明，小噬菌体，特别是单链RNA（ssRNA）左旋病毒，尽管具有进化出的新型PG生物发生抑制剂的能力，但以前却没有得到认可。它们有限的编码潜力。