Brevinin-1

As drug-resistant bacteria have become a serious health problem and have caused thousands of deaths, finding new antibiotics has become an urgent research priority. A novel antimicrobial peptide, named Brevinin-1H, was identified in the skin secretion of Amolops hainanensis through 'shotgun' cloning. It has broad-spectrum antimicrobial activity against tested micro-organisms and has anticancer cell activity. To improve its bioactivity and decrease its cytotoxicity, two structural analogues-Brevinin-1Ha and Brevinin-1HY-were designed based on the secondary structure of the natural peptide. Brevinin-1HY, in which tyrosine substituted Pro11 , had similar activity to the natural peptide against Gram-negative bacteria and cancer cells, but showed a dramatic increase in haemolytic activity and cytotoxicity at its minimum inhibitory concentration. Brevinin-1Ha, which transferred the Rana-box from the C-terminal to a central position, had significantly decreased haemolytic activity, but also in antimicrobial and anticancer activity. The present data suggest that increasing the proportion of α-helix structure in an AMP can increase its target micro-organism bioactivity to some extent.

Host-defense antimicrobial peptides (AMPs) from amphibians are usually considered as one of the most promising next-generation antibiotics because of their excellent antimicrobial properties and low cytotoxicity. In the present study, one novel Brevinin-1 type peptide, Brevinin-1GHd, was isolated and characterized from the skin secretion of the frog, Hylarana guentheri. Brevinin-1GHd was found to possess a wide range of antimicrobial activity through penetrating the bacterial membrane within a short time while showing low hemolysis at bactericidal concentrations, even against the resistant strains. It also inhibited and eradicated biofilms that are thought to be closely related to the rise in resistance. Meanwhile, Brevinin-1GHd exhibited wide-spectrum anti-proliferation activity toward human cancer lines. Taken together, these results indicate that Brevinin-1GHd with its excellent antimicrobial and anticancer activities is a promising candidate for a novel antibiotic agent, and study of its structure-activity relationships also provided a rational template for further research and peptide analog design.

Tuberculosis (TB) is a devastating infectious disease that causes a high rate of mortality. Drugs with new modes of action are needed to overcome this scenario. Cationic antibacterial peptides can serve as a potential alternative to existing TB drugs as they target the entire bacterial membrane for activity, thereby reducing the probability of development of drug resistance. In this study, we report anti-tuberculosis activity of B1CTcu5, a peptide that belongs to brevinin-1 family of antimicrobial peptides. This peptide possesses potent in vitro inhibitory activity against M. tuberculosis at 12.5 μg/mL but was not active against M. smegmatis. B1CTcu5 successfully eliminated intracellular mycobacteria without inducing cytotoxicity to the human macrophages at the concentrations tested. This peptide can be used as a template to design peptide-based anti-tubercular agents.