Recently, the “antimicrobial peptides (AMPs) & antibiotic to substitutes (ATA)” group led by Prof. Wang Jianhua from Feed Research Institute of Chinese Academy of Agricultural Sciences (CAAS) has designed novel antimicrobial peptides against intracellular Salmonella infection by conjugating AMPs with the cell-penetrating peptide via a cleavable linker. These peptides showed higher antimicrobial activity and lower cytotoxicity than the parental peptide, which are candidates for novel antimicrobial agents to treat intracellular pathogens. The study was published in Journal of Medicinal Chemistry.

Salmonella, a major pathogen of zoonosis, can cause severe intestinal infection and diarrhea in humans and animals. Globally, about 1.3 billion people are infected each year, with losses of more than 20 billion dollars. Salmonella can invade and reproduce in host cells; meanwhile, most of the traditional antibiotics show low antibacterial activity due to their low cell penetration rate. AMPs from sea worms have high activity against Salmonella and are not easy to develop resistance, with the high potential for clinical use.

The research results show that the conjugate CNC was generated by connecting the cell-penetrating peptide Tat11 and C-terminal aminated N6 via a cathepsin-cleavable linker to eliminate intracellular Salmonellae Typhimurium. The antibacterial activities of CNC increased by 98% and it had very low hemolysis and cytotoxicity. After treatment with 1−2 μmol/kg of CNC, the survival rate of the S. Typhimurium−infected mice was 66.7−100%, 2-3 folds higher than that of the parental peptide. These results provide a strong theoretical basis for the application of novel AMPs in the prevention and control of intracellular pathogenic bacteria in livestock and poultry.

The study was supported by the National Natural Science Foundation (Grant No.: 31672456, 31572444, 31572445, and 31372346), the AMP Direction of the National Innovation Program of Agricultural Science and Technology in CAAS (Grant No.: CAAS-ASTIP-2013-FRI-02), and its Key Project of Alternatives to Antibiotics for Feed Usages (Grant No.: CAAS-ZDXT2018008). More details are available on the bellow links: https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01079