Identification and functional characterization of ribosomal protein S23 as a new member of antimicrobial protein

Previous studies show that some ribosomal proteins possess antimicrobial peptide (AMP) activity. However, information as such remains rather fragmentary and rather limited. We showed here for the first time that amphioxus RPS23, BjRPS23, was a previously uncharacterized AMP. It not only acted as a pattern recognition receptor, capable of identifying LPS, LTA and PGN, but also an effector, capable of killing the Gram-negative and -positive bacteria. We also showed that the residues positioned at 67–84 formed the core region for the antimicrobial activity of BjRPS23, and its orthologues Verrucomicrobia RPS1268-85 and Thermotoga RPS1265-82 similarly displayed some antibacterial activities. BjRPS23 functioned by a combined action of membranolytic mechanisms including interaction with bacterial membrane via LPS, LTA and PGN, and membrane depolarization. BjRPS23 also stimulated production of intracellular ROS in bacteria. Moreover, we demonstrated that RPS23 existed across widely separated taxa, and might play a universal role in protection against bacterial infection in different animals. In addition, we found that neither BjRPS23 nor its truncated form BjRPS2367-84 were cytotoxic to mammalian cells, making them promising lead molecules for the design of novel peptide antibiotics against bacteria. Collectively, these indicate that RPS23 is a new member of AMP with ancient origin and high conservation. •Amphioxus RPS23, BjRPS23, was shown as a new AMP capable of binding to and killing bacteria.•Residues positioned at 67–84 formed the core region for antimicrobial activity of BjRPS23.•Antibacterial activity of RPS23 was traced back to its prokaryotic homolog RPS12.•BjRPS23 showed membrane selectivity towards bacterial cells but not mammalian cells.