Therapeutic Potential and Mechanism of Action of a New Cathelicidin from the Chacoan Peccary (Catagonus wagneri)

Objective: Proline-rich antimicrobial peptides (PrAMPs) are a specific class of host-defense peptides whose primary mechanism of action involves the inhibition of bacterial ribosomes. The peccaries (Tayassuidae) represent a separate family of non-ruminant even-toed ungulates, belonging to the suborder Suina. Methods: In this study, we used bioinformatics approaches to discover a new cathelicidin from the Chaco peccary (Catagonus wagneri), consisting of 28 amino acid residues and named CwBac28. Its mechanism of action was investigated using a combination of biochemical assays and flow cytometry. Results and Discussion: Although peccaries are evolutionarily closely related to pigs, the closest homologs of the CwBac28 peptide were identified in representatives of the suborder Cetancodonta, which includes the family Hippopotamidae and the infraorder Cetacea. Cathelicidin CwBac28, similar to the well-known bovine PrAMP Bac7, is capable of efficiently inhibiting bacterial translation; however, unlike the latter, it is effective in penetrating bacterial cells lacking the functional transporter protein SbmA without disrupting the integrity of the cytoplasmic membrane of the cells. Conclusions: The broad spectrum of antibacterial activity and demonstrated therapeutic efficacy of CwBac28 in a mouse model of bacterial septicemia make this peptide a promising candidate for the development of new antibiotics.