Antimicrobial activity of PvH4a, a peptide derived from histone H4 of Penaeus vannamei

Abstract

Histones are important players in the formation and transcriptional regulation of eukaryotic nucleosomes. In most vertebrates, histones and histone-derived peptides have also been implicated in antimicrobial activities against various pathogenic microbes. In this study, the sera of Vibrio parahaemolyticus -infected Penaeus vannamei shrimp were filtered through 3 kDa ultrafiltration tubes followed by analysis using reversed-phase high performance liquid chromatography (HPLC). A novel histone H4-derived peptide (TVTAMDVVYALK) was identified and designated as PvH4a. Peptide PvH4a had strong antimicrobial activity against Gram-negative bacteria with the MIC value of 15.6–62.5 μg/mL ( Vibrio. parahaemolyticus, Vibrio fluvialis and Vibrio alginolyticus ) and no effect on Gram-positive bacteria ( Staphylococcus aureus and Streptococcus iniae ). In addition, PvH4a increased the inner-membrane permeability of V. parahaemolyticus concentration-dependently at 1 × MIC and had no adverse effects on normal human hepatocytes (LO2 cells) even at high concentrations (16 × MIC), with a cell survival rate of more than 90.3%. Furthermore, SEM analysis revealed that PvH4a could destroy the cell walls of Gram-negative bacteria as part of its antimicrobial action. Put together, the current findings indicate that during immune response to bacteria infection, shrimp histone H4 generates antimicrobial peptides such as PvH4a as part of the innate immune response. • A novel AMP PvH4a was identified from sera of V. parahaemolyticus -infected P. vannamei . • PvH4a had strong antimicrobial activity against Gram-negative bacteria and no adverse effects on normal human hepatocytes (LO2). • PvH4a comes from the C-terminal of shrimp P. vannamei histone H4. • The antimicrobial activity of PvH4a is executed by increasing the membrane permeability of bacterial.