The Dolphin Proline-Rich Antimicrobial Peptide Tur1A Inhibits Protein Synthesis by Targeting the Bacterial Ribosome

Area of Science:

• Microbiology
• Biochemistry
• Genomics

Background:

• Proline-rich antimicrobial peptides (PrAMPs) are known to internalize into bacteria and disrupt protein synthesis.
• Mammalian PrAMPs have primarily been found in artiodactyls, with limited exploration in related mammalian groups.

Purpose of the Study:

• To identify and characterize novel PrAMPs in cetaceans, specifically the bottlenose dolphin (Tursiops truncatus).
• To investigate the antimicrobial mechanisms of the identified dolphin PrAMPs, Tur1A and Tur1B.

Main Methods:

• Genomic mining of the bottlenose dolphin genome to identify potential PrAMPs.
• Bacterial internalization assays using Escherichia coli with specific inner membrane transporters (SbmA and YjiL/MdM).
• Protein synthesis inhibition assays and X-ray crystallography to determine the mechanism of action.

Main Results:

• Two novel PrAMPs, Tur1A and Tur1B, were identified in the bottlenose dolphin.
• Tur1A, similar to bovine Bac7, internalizes into E. coli via SbmA and YjiL/MdM transporters.
• Tur1A inhibits bacterial protein synthesis by binding to the ribosome and blocking translation initiation-elongation transition.
• Tur1B showed weaker protein synthesis inhibition, suggesting a different mechanism.

Conclusions:

• Bottlenose dolphins possess unique PrAMPs, Tur1A and Tur1B, expanding the known diversity of these antimicrobial peptides.
• Tur1A's mechanism of action, involving ribosome binding and inhibition of protein synthesis, presents a promising avenue for developing novel antimicrobial therapies.
• Structural insights from Tur1A bound to the ribosome can guide the design of new peptide-based antibiotics.