The revitalization of antimicrobial peptides in the resistance era.

Abstract The antibiotic resistance crisis is becoming incredibly thorny due to the indiscriminate employment of antibiotics in agriculture and aquaculture, such as growth promoters, and the emergence of bacteria that are capable of enduring antibiotic treatment in an endless stream. Hence, to reverse this situation, vigorous efforts should be made in the process of identifying other alternative strategies with a lower frequency of resistance. Antimicrobial peptides (AMPs), originated from host defense peptides, are generally produced by a variety of organisms as defensive weapons to protect the host from other pathogenic bacteria. The unique ability of AMPs to control bacterial infections, as well as low propensity to acquire resistance, provides the basis for it to become one of the promising antibacterial substances. Herein, we present new insights into the biological functions, structural properties, distinct mechanisms of action of AMPs and their resistance determinants. Besides, we separately discuss natural and synthetic AMPs, including their source, screening pathway and antibacterial activity. Lastly, challenges and perspectives to identify novel potent AMPs are highlighted, which will expand our understanding of the chemical space of antimicrobials and provide a pipeline for discovering the next-generation of AMPs.