Marine peptides as templates for the design of novel antimicrobials

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Food safety hazards such as foodborne illnesses and antimicrobial resistance are life threatening and urgent global health problem. Given the complexity of the challenge faced at the interface of human and animal health, combined with the impact on the environment, it is crucial to increase the effectiveness of novel antimicrobial agents. Nature is a reservoir for these high-value compounds. Specifically, numerous marine-derived compounds have been proven to harbor antibacterial properties. In previous installment, we revealed the potential of untapped marine species, fishery wastes and crustaceans' by-products, as a promising source of antimicrobial peptides (AMPs), whilst their mode of action has not been entirely determined yet. The time appears opportune for the development of novel classes of antimicrobial agents with less likelihood to gain resistance, which are stable, have modified or extended spectrum of activity, and with limited side effects. The cornerstones of my program are the understanding of mechanisms of action of the novel marine AMPs, the study of combinations and conditions to enhance their potency, the improvement of their antibacterial properties for potential in food production to prevent food spoilage and as antibiotic alternatives in animal feed and human health. This conundrum gives us the opportunity to define an innovative program where the structure-activity relationships of marine novel AMPs can be deciphered at the molecular level which allows identifying the key residues involved in their antibacterial activity. The general hypothesis of this proposal is that structure-activity relationship assays, using an integrated molecular engineering approach, will enhance marine AMPs potency in terms of both stability and antimicrobial activity. The specific objectives will be: 1) To determine the relationship between the primary structure or spatial conformation and antimicrobial activity of marine AMPs, and analogues thereof; 2) To study the marine AMPs-bacterial membrane interaction; 3) To elucidate the molecular mechanisms of synergy between the marine AMPs and study their bacterial membrane leakage potential. Our research activities will unravel the strategies leading to the production of novel AMPs with beneficial properties to encounter public health priority. Government of Canada's response to antimicrobial resistance is laid out in the Federal Action Plan on Antimicrobial resistance and Use in Canada, released in March 2015. With this Action Plan, Canada is particularly well positioned to promote efforts in research to address antimicrobial resistance toward a united global objective in frontiers of microbiological and health concerns.