The Dolphin Proline-Rich Antimicrobial Peptide Tur1A Inhibits Protein Synthesis by Targeting the Bacterial Ribosome. Issue 5 (17th May 2018)

• Record Type: Journal Article
• Authors: Mardirossian, Mario; Pérébaskine, Natacha; Benincasa, Monica; Gambato, Stefano; Hofmann, Sven; Huter, Paul; Müller, Claudia; Hilpert, Kai; Innis, C. Axel; Tossi, Alessandro; Wilson, Daniel N.
• Is Part Of: Cell chemical biology. Volume 25:Issue 5(2018)
• Page Start: 530
• Page End: 539.e7
• Publication Date: 2018-05-17
• Subjects: antibiotic -- cathelicidin -- Bac7 -- dolphin -- PrAMP -- ribosome -- proline-rich antimicrobial peptide -- Tur1A -- Tur1B; Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2018.02.004
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: Proline-rich antimicrobial peptides (PrAMPs) internalize into susceptible bacteria using specific transporters and interfere with protein synthesis and folding. To date, mammalian PrAMPs have so far been identified only in artiodactyls. Since cetaceans are co-phyletic with artiodactyls, we mined the genome of the bottlenose dolphin Tursiops truncatus, leading to the identification of two PrAMPs, Tur1A and Tur1B. Tur1A, which is orthologous to the bovine PrAMP Bac7, is internalized into Escherichia coli, without damaging the membranes, using the inner membrane transporters SbmA and YjiL/MdM. Furthermore, like Bac7, Tur1A also inhibits bacterial protein synthesis by binding to the ribosome and blocking the transition from the initiation to the elongation phase. By contrast, Tur1B is a poor inhibitor of protein synthesis and may utilize another mechanism of action. An X-ray structure of Tur1A bound within the ribosomal exit tunnel provides a basis to develop these peptides as novel antimicrobial agents. Graphical Abstract: Highlights: The proline-rich AMPs Tur1A and Tur1B were identified in the bottlenose dolphin Tur1A is non-lytic and inhibits bacterial protein synthesis Tur1A binds within the ribosomal tunnel and prevents translation elongation Tur1B is a poor inhibitor of translation and thus probably has another target Abstract : Proline-rich antimicrobial peptides (PrAMPs) are antibacterial components of the immune system of some animals. Mardirossian et al. identified two PrAMPs in the artiodactyl Tursiops truncatus (bottlenose dolphin), Tur1A and Tur1B. Tur1A was shown to inhibit bacterial protein synthesis by binding to the ribosome.