Conventional role of ribosomal proteins is ribosome assembly and protein translation, but some ribosomal proteins also show antimicrobial peptide (AMP) activity, though their mode of action remains ill-defined. Here we demonstrated for the first time that amphioxus RPS15, BjRPS15, was a previously uncharacterized AMP, which was not only capable of identifying Gram-negative and -positive bacteria via interaction with LPS and LTA but also capable of killing the bacteria. We also showed that both the sequence and 3D structure of RPS15 and its prokaryotic homologs were highly conserved, suggesting its antibacterial activity is universal across widely separated taxa. Actually this was supported by the facts that the residues positioned at 45–67 formed the core region for the antimicrobial activity of BjRPS15, and its prokaryotic counterparts, including Nitrospirae RPS19₃₃₋₅₅, Aquificae RPS19₃₃₋₅₅ and P. syringae RPS19_50-72, similarly displayed antibacterial activities. BjRPS15 functioned by both interaction with bacterial surface via LPS and LTA and membrane depolarization as well as induction of intracellular ROS. Moreover, we showed that RPS15 existed extracellularly in amphioxus, shrimp, zebrafish and mice, hinting it may play a critical role in systematic immunity in different animals. In addition, we found that neither BjRPS15 nor its truncated form BjRPS15_45–67 were toxic to mammalian cells, making them promising lead molecules for the design of novel AMPs against bacteria. Collectively, these indicate that RPS15 is a new member of AMP with ancient origin and high conservation throughout evolution.

核糖体蛋白的常规作用是核糖体组装和蛋白翻译，但是一些核糖体蛋白也显示出抗菌肽（AMP）活性，尽管它们的作用方式仍然不清楚。在这里，我们首次证明了双歧杆菌RPS15 BjRPS15是以前未表征的AMP，它不仅能够通过与LPS和LTA相互作用来鉴定革兰氏阴性和阳性细菌，而且能够杀死细菌。我们还显示，RPS15的序列和3D结构及其原核同源物均高度保守，表明其抗菌活性在广泛分离的类群中具有普遍性。实际上，这一事实得到了以下事实的支持：位于45-67位的残基形成了BjRPS15及其原核生物对应物（包括硝基螺_菌RPS19 _33-55，水曲霉RPS19 _33-55和丁香假单胞菌RPS19 _50-72同样显示出抗菌活性。BjRPS15通过LPS和LTA与细菌表面相互作用和膜去极化以及诱导细胞内ROS发挥功能。此外，我们发现RPS15在两栖类，虾，斑马鱼和小鼠的细胞外存在，暗示它可能在不同动物的系统免疫中起关键作用。此外，我们发现BjRPS15或其截短形式BjRPS15 _45-67对哺乳动物细胞具有毒性，使其成为有前途的铅分子，可用于设计新型的针对细菌的AMP。总的来说，这些表明RPS15是AMP的新成员，具有古老的起源和在整个进化过程中的高度保护性。