A teleost bactericidal permeability-increasing protein-derived peptide that possesses a broad antibacterial spectrum and inhibits bacterial infection as well as human colon cancer cells growth

The bactericidal permeability-increasing protein (BPI) is a multifunctional cationic protein produced by neutrophils with antibacterial, antitumor, and LPS-neutralizing properties. In teleost, a number of BPIs have been reported, but their functions are very limited. In this study, an N-terminal peptide, BO18 (with 18 amino acids), derived from rock bream (Oplegnathus fasciatus) BPI, was synthesized and investigated for its antibacterial spectrum, action mechanism, immunoregulatory property as well as the inhibition effects on bacterial invasion and human colon cancer cells growth. The results showed that BO18 was active against Gram-positive bacteria Bscillus subiilis, Micrococcus luteus, and Staphylococcus aureus, as well as Gram-negative bacteria Vibrio alginolyticus, Vibrio litoralis, Vibrio parahaemolyticus and Vibrio vulnificus. BO18 treatment facilitated the bactericidal process of erythromycin and rifampicin by enhancing the permeability of the outer membrane. During its interaction with V. alginolyticus, BO18 exerted its antibacterial activity by destroying cell membrane integrity, penetrating into the cytoplasm and binding to genomic DNA and total RNA. In vitro analysis indicated BO18 could enhance the respiratory burst ability and regulate the expression of immune related genes of macrophages. In vivo detection showed the administration of fish with BO18 before bacterial infection significantly reduced pathogen dissemination and replication in tissues. In addition, BO18 exerted a cytotoxic effect on the growth of human colon cancer cells HT-29. Together, these results add new insights into the function of teleost BPIs, and support that BO18 is a novel and broad-spectrum antibacterial peptide with potential to apply in fighting pathogenic infection in aquaculture. •A rock bream BPI derived peptide BO18 was active against both Gram-positive and Gram-negative bacteria.•BO18 destroyed cell membrane integrity, penetrated into the cytoplasm, and bound with the nucleic acids.•BO18 enhanced the respiratory burst and regulated the immune related genes expression of macrophages.•BO18 inhibited bacterial invasion in olive flounder.•BO18 exerted a cytotoxic effect on human colon cancer cells HT-29.